Objective To explore the efficacy of blunt separation method in midline catheter intubation in elderly patients with coagulation dysfunction.Methods A total of 80 elderly patients with coagulation dysfunction were selected in the convenience sampling method from October 2022 to April 2023 in our hospital,and they were randomly divided into an experimental(blunt)group and a control(routine)group,with 40 patients in each group.The differences in the degree of bleeding and exudation at the puncture site,the pain score and the incidence of complications(including bleeding and exudation,phlebitis,symptomatic catheter-related thrombus,catheter blockage,catheter pulling-off)were compared between 2 groups.Results In the experimental group,the degree of bleeding and exudation at the puncture point immediately after the operation,degree of bleeding and exudation at the puncture point 24 hours after the operation,pain score 1 day after the catheterization,pain score 3 days after the catheterization,incidence of bleeding and exudation,total incidence of complications and maintenance times were significantly lower than these in the control group(P＜0.05).In terms of the pain score immediately after the operation,pain score 5 days after the operation,incidence of phlebitis,incidence of symptomatic catheter-related thrombosis,incidence of catheter blockage,incidence of catheter pulling-off,incidence of catheter related skin injury,incidence of unplanned extubation,success rate of one-time sheath delivery and the indwelling time,the differences between the experimental group and control group were not significant(P＜0.05).Conclusion The application of blunt separation method in midline catheter indwelling can significantly reduce the incidence and degree of bleeding at the puncture point,decrease the maintenance times and relieve the pain in elderly patients with coagulation dysfunction.

Purpose::Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.Methods::C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. Results::Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.Conclusions::Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective To observe the clinical efficacy of"triple-posture positive bone-setting"chiropractic manipulation combined with Tongluo Huoxue Formula for the treatment of lumbar spinal stenosis(LSS)with qi deficiency and blood stasis syndrome.Methods Sixty patients with LSS of qi deficiency and blood stasis type were randomly divided into trial group and control group,with 30 cases in each group.The trial group was treated with"triple-posture positive bone-setting"chiropractic manipulation(a chiropractic manipulation performed under the positive cooperation of the patients at three postures)combined with Tongluo Huoxue Formula,while the control group was treated with"triple-posture positive bone-setting"chiropractic manipulation combined with conventional western medicine.The course of treatment for the two groups covered 4 weeks.Before and after treatment,the patients of the two groups were observed in the changes of pain visual analogue scale(VAS)score,Japanese Orthopedic Association(JOA)score of lumbar function,Oswestry Disability Index(ODI)score,straight-leg raising test results and serum interleukin 6(IL-6)and C-reactive protein(CRP)levels.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the trial group was 96.67％(29/30)and that of the control group was 63.33％(19/30).The intergroup comparison(tested by Fisher's exact test)showed that the clinical efficacy of the trial group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the lumbar function indicators of pain VAS scores and ODI scores in the trial group were significantly lower(P＜0.05),and the JOA scores were significantly higher than those before treatment(P＜0.05),while in the control group,only the ODI scores were significantly lower than those before treatment(P＜0.05).The intergroup comparison showed that the decrease of VAS and ODI scores and the increase of JOA scores in the trial group were significantly superior to those in the control group(P＜0.05 or P＜0.01).(3)After treatment,the Laseque s sign of the trial group was significantly improved compared with that before treatment(P＜0.05),while no significant improvement was presented in the control group(P＞0.05).The intergroup comparison showed that the improvement of Laseque's sign in the trial group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the levels of serum inflammatory factors of IL-6 and CRP in the two groups were lower than those before treatment(P＜0.05),and the decrease of serum IL-6 level in the trial group was significantly superior to that in the control group(P＜0.05),but CRP level in the two groups after treatment did not differ from that before treatment,no statistically significant difference was shown between the two groups after treatment,either(P＞0.05).(5)The incidence of adverse reactions in the trial group was 6.67％(2/30)and that in the control group was 13.33％(4/30),and the intergroup comparison(by Fisher's exact test)showed that there was no significant difference between the two groups(P＞0.05).Conclusion The therapeutic effect of"triple-posture positive bone-setting"chiropractic manipulation combined with Tongluo Huoxue Formula exert certain effect for the treatment of LSS patients with qi deficiency and blood stasis syndrome,and it has more obvious advantages in improving the lumbar function,promoting the rehabilitation of the patients,and lowering the level of serum inflammatory factors than"triple-posture positive bone-setting"chiropractic manipulation combined with conventional western medication.

Objective To evaluate the methodological and reporting quality of published guidelines/consensus for childhood autism(CA),providing a basis for formulating domestic CA guidelines.Methods We searched databases including CNKI,Wanfang Data,SinoMed,Medlive,PubMed,national institute of health and clinical excellence(NICE),national guideline clearinghouse(NGC),and Scottish intercollegiate guidelines network(SIGN)for Chinese and foreign guideline/consensus on childhood autism published before February 1,2024.Two researchers independently evaluated the methodology and reporting quality of the guideline/consensus using the Appraisal of Guidelines Research and Evaluation Ⅱ(AGREE Ⅱ)and Reporting Items for Practice Guidelines in Healthcare(RIGHT)tools.Results After literature screening,19 CA guidelines/consensus were included,comprising 11 guidelines,7 consensus,and 1 expert recommendation,with 9 domestic and 10 foreign articles.The AGREE Ⅱ evaluation scores for the six domains were as follows:scope and purpose(91.1％±4.5％),stakeholder involvement(86.8％±6.7％),rigour of development(83.0％±10.2％),clarity of presentation(84.3％±6.2％),applicability(82.7％±13.3％),and editorial independence(65.4％±21.8％).The RIGHT checklist reported rates for the seven domains were:basic information(87.6％±11.0％),background(87.6％±13.8％),evidence(81.1％±22.6％),recommendation(71.1％±38.4％),review and quality assurance(83.5％±16.7％),funding and declaration and management of interests(48.7％±29.4％),and other information(64.4％±11.8％).The domain with the lowest score for methodological quality was"editorial independence"and for reporting quality,it was"funding and declaration and management of interests".The reporting rate of domestic articles(26.2％±1.5％)was significantly lower than that of foreign articles(52.6％±2.2％),with a statistically significant difference(P<0.05).Conclusion The overall quality of current childhood autism guidelines/consensus requires improvement.During the formulation and reporting of guidelines/consensus,strictly adhering to AGREE Ⅱ and RIGHT is imperative,and it is essential to clearly report funding sources and conflicts of interest.

Objective:To compare the therapeutic effects of 0.05% cyclosporine and 0.1% fluorometholone eye drops in patients with moderate and severe dry eye.Methods:A randomized controlled study was conducted.Fifty-two patients (52 eyes) with moderate to severe dry eye in Tianjin Medical University Eye Hospital from August 2021 to December 2022 were enrolled and randomly divided into 0.05% cyclosporine group and 0.1% fluorometholone group by random number table method, with 26 cases (26 eyes) in each group.Patients received 0.05% cyclosporine eye drops (2 times/day) and 0.1% fluorometholone eye drops (2 times/day) combined with calf blood deproteinized extract eye drops (4 times/day) according to the grouping.Before and 1, 3 and 6 months after treatment, clinical symptoms and signs were observed and Ocular Surface Disease Index (OSDI) score, corneal fluorescein staining (CFS) score, Schirmer Ⅰ test (SⅠT), non-invasive first tear film break-up time (NIBUTf), and conjunctival goblet cell (CGC) density were recorded.Before treatment and after 6 months of treatment, changes in corneal nerves and dendritic cells (DC) were observed by in vivo confocal microscopy (IVCM).This study adhered to the Declaration of Helsinki and was approved by the Medical Ethics Committee of Eye Hospital of Tianjin Medical University (No.2021KY-17).Written informed consent was obtained from each subject. Results:Compared with the 0.1% fluorometholone group, CFS score decreased after 1 month of treatment, but SⅠT, NIBUTf and CFS score increased after 3 months of treatment, and OSDI score, SⅠT and CFS score decreased after 6 months of treatment in the 0.05% cyclosporine group, showing statistically significant differences (all at P<0.05).Compared with baseline, in the 0.05% cyclosporine group, NIBUTf increased and CFS score decreased after 1 month of treatment, OSDI score and CFS score decreased, SⅠT and NIBUTf increased after 3 and 6 months of treatment, showing statistically significant differences (all at P<0.05).In the 0.1% fluorometholone group, CFS score decreased after 3 months of treatment, OSDI score and CFS score decreased, SⅠT increased after 6 months of treatment compared to baseline, showing statistically significant differences (all at P<0.05).OSDI score and CFS score decreased, SⅠT increased after 6 months of treatment compared to 3 months of treatment in the 0.05% cyclosporine group, and the differences were statistically significant (all at P<0.05).Baseline and CGC densities after 1, 3 and 6 months of treatment were (147.66±17.29), (195.44±15.46), (210.36±19.15) and (282.09±22.63)cells/mm 2 in the 0.05% cyclosporine group and (138.09±17.29), (95.67±15.46), (117.77±19.15) and (109.13±22.63)cells/mm 2 in the 0.1% fluorometholone group, respectively, with a statistically significant overall difference ( Fgroup=11.724, P<0.001; Ftime=4.837, P=0.005).Compared with the 0.1% fluorometholone group, CGC density in the 0.05% cyclosporine group increased after 1, 3 and 6 months of treatment, with statistically significant differences (all at P<0.05).Compared with baseline, the CGC density increased in the 0.05% cyclosporine group after 1, 3 and 6 months of treatment, and the differences were statistically significant (all at P<0.05).Compared with the 0.1% fluorometholone group, the corneal nerve fiber density in the 0.05% cyclosporine group increased after 6 months of treatment, and corneal DC density, area and dendrite number decreased, showing statistically significant differences (all at P<0.05). Conclusions:Cyclosporine 0.05% eye drops combined with calf blood deproteinized extract eye drops can improve symptoms and signs in patients with moderate to severe dry eye, and the long-term effect is better than that of 0.1% fluorometholone plus calf blood deproteinized extract eye drops.

Objective:To investigate the effects of dexmedetomidine(DEX)on the malignant biological behavior of gastric cancer(GC)cells through the immune regulation mechanism mediated by cyclic GMP-AMP synthase-stimulator of interferon gene(cGAS-STING)pathway.Methods:GC cell line MGC-803 was randomly divided into Control group(blank medium treatment),DEX low concentration group(DEX-L group,1 ng/ml),DEX medium concentration group(DEX-M group,10 ng/ml),DEX high concentra-tion group(DEX-H group,100 ng/ml)and DEX high concentration+cGAS inhibitor RU.521 group(DEX-H+RU.521 group,100 ng/ml DEX+1.0 μmol/L RU.521).Cell proliferation was detected by CCK-8 method.Cell scratch test was used to detect the migration ability of cells in each group.Transwell test was used to detect the invasive ability of cells in each group.The apoptosis rate was detected by flow cytometry.The levels of IL-2,interferon gamma(IFN-γ)and tumor necrosis factor alpha(TNF-α)in cells were detected by ELISA.Real time-fluorescent quantitative PCR(RT-qPCR)was applied to detect the expression levels of cGAS,STING and interferon typeⅠ(IFN-Ⅰ)mRNA.Western blot was used to detect the expressions of cGAS,STING,Bax,CyclinD1,matrix metalloproteinase 9(MMP9),N-cadherin,Vimentin,E-cadherin,Caspase3,Caspase8 and their shear type and phosphorylation level of TANK-binding kinase 1(TBK1)and interferon regulatory factor 3(IRF3).Results:Compared with Control group,the cell migration rate,number of cell invasions,TNF-α level,CyclinD1,MMP9,N-cadherin,Vimentin protein expressions in MGC-803 cells in DEX-M and DEX-H groups were decreased obviously(P<0.05),the growth inhibition rate(48 h,72 h),apoptosis rate,IL-2,IFN-γ,Bax,E-cadherin,Cleaved Caspase3,Cleaved Caspase8 protein expression levels,cGAS,STING,IFN-Ⅰ mRNA levels and protein expression levels and phosphorylation levels of TBK1 and IRF3 were increased obviously(P<0.05).RU.521 weakened the inhibitory effects of DEX on the proliferation,migration and invasion of GC cells and the ability to induce apoptosis,and alleviated the improvement on immune function.Conclusion:DEX may inhibit the proliferation,migration and invasion of GC cells and induce apoptosis of GC cells by acti-vating cGAS-STING pathway mediated immune regulation.

Objective:To explore the effects of swallowing rehabilitation training on swallowing function and quality of life in patients after laryngectomy.Methods:Randomized controlled trials on the effects of swallowing rehabilitation training on swallowing function and quality of life in postoperative laryngeal cancer patients were electronically retrieved from the Cochrane Library, PubMed, Embase, Web of Science, CINAHL, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biology Medicine disc. The search period was from database establishment to February 1, 2024. The quality evaluation criteria for randomized controlled trials of Joanna Briggs Institute Evidence-Based Health Care Center (2016) was used to evaluate the included literature. RevMan 5.3 software was used for meta-analysis.Results:A total of ten articles were included, with 987 patients. Meta-analysis showed that swallowing rehabilitation training could improve the swallowing function ( P<0.01) and quality of life ( P<0.01) of patients after laryngectomy. Conclusions:Swallowing rehabilitation training can improve patients' swallowing function and quality of life after laryngectomy and is worth applying in clinical practice.

This work was aimed at predicting and verifying B-cell epitopes of SARS-CoV-2 E protein through bioinformatics methods,and clarifying the dominant B cell epitopes with mouse polyclonal antibody serum prepared through SARS-CoV-2 re-combinant E protein immunization and human positive serum vaccinated with inactivated SARS-CoV-2 vaccine.The structural and B-cell linear epitopes of SARS-CoV-2 E protein were predicted with SOPMA,Expasy,SWISS-MODEL,IEDB database,and Bepid-2.0 software.Candidate epitopes were expressed as GST-tagged recombinant protein fragments in an E.coli sys-tem,and their immunoreactivity with mouse and human poly-clonal positive serum against SARS-CoV-2 E protein was de-tected by western blotting and indirect ELISA,respectively.The epitope prediction results showed that E protein contained linear B cell epitopes Ser6-Val14 and Tyr57-Pro71,and the conformational epitopes of Glu8-Val12,Leu39-Tyr59,and Ser60-Leu65.The GST tagged recombinant E protein fragments of E1 and E3,containing Ser6-Val14 and Tyr57-Pro71 epitopes,respectively,as well as E2 without an epitope sequence as a control,were expressed in an E.coli expression system and successfully purified with an Ni-NTA column.Western blotting and indirect ELISA analysis indicated that all mouse and human SARS-CoV-2 positive sera positively reacted with only E1 and E3 proteins,but negatively reacted with E2 protein,thus indicating that the corresponding epitope prediction with Ser6-Val14 and Tyr57-Pro71 was correct.This study successfully predicted and preliminarily identified two linear B cell epitopes of SARS-CoV-2 E protein,thus providing a reference for the preparation of new coronavirus vaccines and the analysis of immune response characteristics.

Aim To investigate the involvement of mesencephalic astrocyte-derived neurotrophic factor(MANF)in rifampicin(RFP)-induced cholestatic liv-er injury.Methods We investigated the impact of MANF gene deletion on rifampicin-induced BAT ex-pression in mice by the MANF gene knockout mouse model.We investigated the influence of MANF knock-down on nuclear factor erythroid 2-related factor 2(Nrf2)in HepG2 cells by the MANF knockdown cell model.Results Compared with the wild-type(WT)mice,the mRNA and protein expression levels of bile salt export pump(BSEP)and multidrug-resistant asso-ciated protein4(MRP4)significantly increased in WT mice treated with RFP.However,compared to the WT mice treated with RFP,the mRNA and protein expres-sion levels of BSEP,Multidrug resistance protein 1(MDR1),multidrug resistance associated proteins 2/3/4(MRP2/3/4),and organic solute transport pro-teins α(OST α)were significantly reduced.In cell experiments we found that MANF knockdown weakened the expression of Nrf2 and its nuclear translocation by RFP.Conclusion MANF may regulate adaptive BAT expression by modulating Nrf2 expression,thereby pla-ying a protective role in RFP-induced liver injury.