Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

Cognitive impairment in cerebral small vessel disease induced by hypertension

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

Association of prealbumin with short-term and long-term outcomes in patients with acute ST-segment elevation myocardial infarction

BACKGROUND Prealbumin is considered to be a useful indicator of nutritional status. Furthermore, it has been found to be associated with severities and prognosis of a range of diseases. However, limited data on the association of baseline prealbumin level with outcomes of patients with acute ST-segment elevation myocardial infarction(STEMI) are available.METHODS We analyzed 2313 patients admitted for acute STEMI between October 2013 and December 2020. In-hospital outcomes and mortality during the 49 months(interquartile range: 26–73 months) follow-up period were compared between patients with the low prealbumin level(< 170 mg/L) and those with the high prealbumin level(≥ 170 mg/L).RESULTS A total of 114 patients(4.9%) died during hospitalization. After propensity score matching, patients with the low prealbumin level than those with the high prealbumin level experienced higher incidences of heart failure with Killip class Ⅲ(9.9%vs. 4.4%, P = 0.034), cardiovascular death(8.4% vs. 3.4%, P = 0.035) and the composite of major adverse cardiovascular events(19.2%vs. 10.3%, P = 0.012). Multivariate logistic regression analysis identified that the low prealbumin level(< 170 mg/L) was an independent predictor of in-hospital major adverse cardiovascular events(odds ratio = 1.918, 95% CI: 1.250–2.942, P = 0.003). The cutoff value of prealbumin level for predicting in-hospital death was 170 mg/L(area under the curve = 0.703, 95% CI: 0.651–0.754, P< 0.001;sensitivity = 0.544, specificity = 0.794). However, after multivariate adjustment of possible confounders, baseline prealbumin level(170 mg/L) was no longer independently associated with 49-month cardiovascular death. After propensity score matching, Kaplan-Meier survival curves revealed consistent results.CONCLUSIONS Decreased prealbumin level closely related to unfavorable short-term outcomes. However, after multivariate adjustment and controlling for baseline differences, baseline prealbumin level was not independently associated with an increased risk of long-term cardiovascular mortality in STEMI patients.

Effect of cytochrome P4502C19(CYP2C19)gene polymorphism and clopidogrel reactivity on long term prognosis of patients with coronary heart disease after PCI

Objective To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with longterm clinical outcome in patients with coronary heart disease(CHD)undergoing percutaneous coronary intervention(PCI).Methods In total,675 patients were enrolled.Based on the platelet inhibition rate,patients were categorized into two groups:clopidogrel low responsiveness(CLR)and normal clopidogrel responsiveness(NCR).The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up treatment.Patients were classified into three groups(normal metabolizer,intermediate metabolizer,and poor metabolizer)based on the CYP2C19 genotype.We aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity.The cumulative rates of 12-month all-cause deaths,major adverse cardiovascular events(MACCEs),and bleeding events were calculated.Results CLR was observed in 44.4%of the overall population.Significant differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes(P<0.05).At the 12-month follow-up,13 patients(1.9%)died and 96 patients(14.2%)experienced MACCEs.Patients with CLR(9.6%vs.11.7%vs.22.1%,P<0.05)or poor metabolizer(10.7%vs.16.4%vs.22.6%,P=0.026)experienced a higher rate of MACCEs.A MACCEs risk score between zero and two was calculated.The highest incidence of MACCEs significantly increased with the 2-positive results,and the area under the curve(AUC)was 0.712(95%CI:0.650-0.774,P<0.05).There was no significant difference between the group with a score of one and the occurrence of MACCEs(P>0.05).Conclusions Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene polymorphism.CYP2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI,which is better than either test alone.

Meta-analysis of factors influencing anterior knee pain after total knee arthroplasty

BACKGROUND Total knee arthroplasty(TKA)is a mature procedure recommended for correcting knee osteoarthritis deformity,relieving pain,and restoring normal biomechanics.Although TKA is a successful and cost-effective procedure,patient dissatisfaction is as high as 50%.Knee pain after TKA is a significant cause of patient dissatisfaction;the most common location for residual pain is the anterior region.Between 4%and 40%of patients have anterior knee pain(AKP).AIM To investigate the effect of various TKA procedures on postoperative AKP.METHODS We searched PubMed,EMBASE,and Cochrane from January 2000 to September 2022.Randomized controlled trials with one intervention in the experimental group and no corresponding intervention(or other interventions)in the control group were collected.Two researchers independently read the title and abstract of the studies,preliminarily screened the articles,and read the full text in detail according to the selection criteria.Conflicts were resolved by consultation with a third researcher.And relevant data from the included studies were extracted and analyzed using Review Manager 5.4 software.RESULTS There were 25 randomized controlled trials;13 were comparative studies with or without patellar resurfacing.The meta-analysis showed no significant difference between the experimental and control groups(P=0.61).Six studies were comparative studies of circumpatellar denervation vs non-denervation,divided into three subgroups for meta-analysis.The two-subgroup meta-analysis showed no significant difference between the experimental and the control groups(P=0.31,P=0.50).One subgroup meta-analysis showed a significant difference between the experimental and control groups(P=0.001).Two studies compared fixed-bearing TKA and mobile-bearing TKA;the results meta-analysis showed no significant difference between the experimental and control groups(P=0.630).Two studies compared lateral retinacular release vs non-release;the meta-analysis showed a significant difference between the experimental and control groups(P=0.002);two other studies compared other factors.CONCLUSION Patellar resurfacing,mobile-bearing TKA,and fixed-bearing TKA do not reduce the incidence of AKP.Lateral retinacular release can reduce AKP;however,whether circumpatellar denervation can reduce AKP is controversial.

2023 Guideline for the management of hypertension in the elderly population in China

Preamble Hypertension is one of the most common chronic diseases and the primary risk factor for stroke,myocardial infarction and even cardiovascular death.More than half of the elderly population has high blood pressure.Elderly people are a unique group,and strategies for the prevention,diagnosis,evaluation,and treatment of hypertension in elderly individuals differ significantly from those in the general population.

Standard-definition White-light,High-definition White-light versus Narrow-band Imaging Endoscopy for Detecting Colorectal Adenomas:A Multicenter Randomized Controlled Trial

Objective This study aimed to compare the performance of standard-definition white-light endoscopy(SD-WL),high-definition white-light endoscopy(HD-WL),and high-definition narrow-band imaging(HD-NBI)in detecting colorectal lesions in the Chinese population.Methods This was a multicenter,single-blind,randomized,controlled trial with a non-inferiority design.Patients undergoing endoscopy for physical examination,screening,and surveillance were enrolled from July 2017 to December 2020.The primary outcome measure was the adenoma detection rate(ADR),defined as the proportion of patients with at least one adenoma detected.The associated factors for detecting adenomas were assessed using univariate and multivariate logistic regression.Results Out of 653 eligible patients enrolled,data from 596 patients were analyzed.The ADRs were 34.5%in the SD-WL group,33.5%in the HD-WL group,and 37.5%in the HD-NBI group(P=0.72).The advanced neoplasm detection rates(ANDRs)in the three arms were 17.1%,15.5%,and 10.4%(P=0.17).No significant differences were found between the SD group and HD group regarding ADR or ANDR(ADR:34.5%vs.35.6%,P=0.79;ANDR:17.1%vs.13.0%,P=0.16,respectively).Similar results were observed between the HD-WL group and HD-NBI group(ADR:33.5%vs.37.7%,P=0.45;ANDR:15.5%vs.10.4%,P=0.18,respectively).In the univariate and multivariate logistic regression analyses,neither HD-WL nor HD-NBI led to a significant difference in overall adenoma detection compared to SD-WL(HD-WL:OR 0.91,P=0.69;HD-NBI:OR 1.15,P=0.80).Conclusion HD-NBI and HD-WL are comparable to SD-WL for overall adenoma detection among Chinese outpatients.It can be concluded that HD-NBI or HD-WL is not superior to SD-WL,but more effective instruction may be needed to guide the selection of different endoscopic methods in the future.Our study’s conclusions may aid in the efficient allocation and utilization of limited colonoscopy resources,especially advanced imaging technologies.

Brain-wide activation involved in 15 mA transcranial alternating current stimulation in patients with first-episode major depressive disorder

Background Although 15 mA transcranial alternating current stimulation(tACS)has a therapeutic effect on depression,the activations of brain structures in humans accounting for this tACS configuration remain largely unknown.Aims To investigate which intracranial brain structures are engaged in the tACS at 77.5 Hz and 15 mA,delivered via the forehead and the mastoid electrodes in the human brain.Methods Actual human head models were built using the magnetic resonance imagings of eight outpatient volunteers with drug-naïve,first-episode major depressive disorder and then used to perform the electric field distributions with SimNIBS software.Results The electric field distributions of the sagittal,coronal and axial planes showed that the bilateral frontal lobes,bilateral temporal lobes,hippocampus,cingulate,hypothalamus,thalamus,amygdala,cerebellum and brainstem were visibly stimulated by the 15 mA tACS procedure.Conclusions Brain-wide activation,including the cortex,subcortical structures,cerebellum and brainstem,is involved in the 15 mA tACS intervention for first-episode major depressive disorder.Our results indicate that the simultaneous involvement of multiple brain regions is a possible mechanism for its effectiveness in reducing depressive symptoms.

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).

Effect of coronary artery revascularization on in-hospital outcomes and long-term prognoses in acute myocardial infarction patients with prior ischemic stroke

ObjectiveTo 调查冠的动脉 revascularization 治疗(大车)，包括的经皮的冠的干预(一种总线标准)和冠的动脉是否绕过 grafting ( CABG )，能为有优先的 ischemic 的病人摸的尖锐心肌的梗塞( AMI )改进在里面医院和长期的结果() 387 个 AMI 病人与的 .MethodsA 总数优先在这队研究从2005年1月15日连续地被注册到2011年12月24日。所有病人被分成 CART 组(n = 204 ) 或保守的药(厘米) 组(n = 183 ) 。在里面医院 cardiocerebral 事件和在 36 个月的平均后续以后的二个组的长期的死亡被 Kaplan-Meier 幸存曲线记录并且由逻辑回归和艇长回归 model.ResultsThe 大车病人比较了更年轻(66.5 &#x000b1；9.7 年对 71.7 &#x000b1；9.7 年， P &#x0003c；0.01 ) ，有更少的非圣片断举起心肌的梗塞(11.8% 对 20.8% ， P = 0.016 ) 并且更多重脉管的冠的损害(50% 对 69.4% ， P = 0.031 ) 。当 26.2% 在 CM 组织时，在 CART 组的 cardiocerebral 事件的住院发生是 9.3%(P &#x0003c；0.01 ) 。大车显著地在 65% 减少了在里面医院 cardiocerebral 事件的风险[调整机会比率(或)= 0.35， 95% CI：0.13-0.92 ] 。在后续底， 57 个盒子(41.6%) 在厘米组死了(n = 137 ) 并且 24 个盒子(12.2%) 在大车组死了(n = 197 ) 。考克斯回归显示那辆大车减少了在 72% 的长期的死亡[调整危险比率(HR )= 0.28， 95% CI：0.06-0.46 ] ，当范畴的分析显示了时，一种总线标准和 CABG.ConclusionsCART 之间的重要差别都没在为 AMI 病人改进在里面医院和长期的预测与上有重要效果优先。

Long-term prognosis and prognostic determinants of patients with first attack of mild and moderate ischemia at Beijing community hospitals

A total of 710 patients with first-ever ischemic stroke were consecutively recruited between January 2003 and December 2004 from five community hospitals/stations in five districts of Beijing, China. As of December 31, 2008, a total of 2 477 person-years were followed-up. During the five-year follow-ups, 117 adverse events occurred, including all-cause death and acute cardiovascular events （recurrent stroke, acute myocardial infarction, and sudden death）. The five-year cumulative mortality rate was 2.18/100 person-years （54 cases）, with 3.88/100 person-years （96 cases） of acute cardiovascular events and 3.02/100 person-years （75 cases） of recurrent stroke. Multiple factor analyses using the Cox proportional hazards ratio models showed that age, diabetes, and dependence of activities of daily living were independent predictors for death, acute cardiovascular disease events, or recurrent stroke. The results demonstrated that recurrent stroke was a major vascular disease that affected the prognosis of mild or moderate stroke patients. Secondary prevention of stroke patients should include active management of vascular risk factors and rehabilitation.

Incidence,predictors and prognosis of acute kidney injury in acute ST-segment elevation myocardial infarction patients undergoing emergent coronary angiography/primary percutaneous coronary intervention

BACKGROUND Acute kidney injury(AKI) after coronary angiography(CAG) and primary percutaneous coronary intervention(PPCI) is frequently observed, and often interpreted as contrast induced-AKI. This study aimed to investigate the incidence, predictors and outcomes of AKI in acute ST-segment elevation myocardial infarction(STEMI) patients undergoing emergent CAG/PPCI using the control group of STEMI patients who were not exposed to contrast agents within the first 72 h.METHODS We performed a retrospective analysis of 1670 STEMI patients. Of them, 673 patients underwent emergent CAG/PPCI, and 997 patients treated with thrombolysis or no reperfusion therapy who were not exposed to contrast material during the first 72 h. AKI was defined as an increase of serum creatinine ≥ 44.2 mmol/L or ≥ 25% from baseline within 72 h. Patents were then followed up for the occurrence of all-cause mortality for 40 months(interquartile range: 24–55 months).RESULTS After propensity score matching, 505 pairs of patients were matched. Overall, the incidence of AKI was 27.4%, and AKI rates were not significantly different in patients with and without emergent CAG/PPCI procedure(27.5% vs. 27.3%, P = 0.944). Multivariate logistic regression analysis identified that the independent predictors of AKI were female, elevated interleukin-6 level,decreased lymphocyte count, left ventricular ejection fraction < 50% and use of diuretics in patients with emergent CAG/PPCI. Patients with AKI than those without AKI experienced higher incidence of acute heart failure with Killip class Ⅲ(9.4% vs. 3.3%, P =0.005;15.2% vs. 6.8%, P = 0.003, respectively) and mortality(5.8% vs. 1.4%, P = 0.014;12.3% vs. 4.6%, P = 0.002, respectively) in patients with and without emergent CAG/PPCI. Multivariate Cox regression analysis confirmed that AKI was independently associated with long-term mortality rate at 40 months follow-up in patients with and without emergent CAG/PPCI(HR = 1.867, 95% CI:1.086–3.210, P = 0.024;HR = 1.700, 95% CI: 1.219–2.370, P = 0.002, respectively).CONCLUSIONS Approximately 27.0% of STEMI patients experience AKI, which is strongly associated with an increased shortand long-term mortality regardless of emergent CAG/PPCI procedure. The development of AKI is mainly related to female gender, inflammation reaction, heart failure and use of diuretics in STEMI patients undergoing emergent CAG/PPCI.

Association of bone turnover biomarkers with severe intracranial and extracranial artery stenosis in type 2 diabetes mellitus patients

BACKGROUND Intracranial and extracranial artery stenosis is associated with cerebral infarction.Vascular calcification and atherosclerosis are the main causes of stenosis and major risk factors for cardiovascular and cerebrovascular events in patients with type 2 diabetes mellitus(T2DM).Bone turnover biomarkers(BTMs)are associated with vascular calcification,atherosclerosis,glucose,and lipid metabolism.AIM To investigate the association of circulating BTM levels with severe intracranial and extracranial artery stenosis in patients with T2DM.METHODS For this cross-sectional study including 257 T2DM patients,levels of the BTMs serum osteocalcin(OC),C-terminal cross-linked telopeptide of type I collagen(CTX),and procollagen type I N-peptide were measured by electrical chemiluminescent immunoassay,and artery stenosis was assessed by color Doppler and transcranial Doppler.Patients were grouped according to the existence and location(intracranial vs.extracranial)of artery stenosis.Correlations between BTM levels,previous stroke,stenosis location,and glucose and lipid metabolism were analyzed.RESULTS T2DM patients with severe artery stenosis had a higher frequency of previous stroke and levels of all three tested BTMs(all P<0.05)than patients without.Some differences in OC and CTX levels were observed according to the location of artery stenosis.Significant associations were also observed between BTM levels and some glucose and lipid homeostasis parameters.On multivariate logistic regression analysis,all BTMs were significant predictors of artery stenosis in T2DM patients with and without adjustment for confounding factors(all P<0.001),and receiver operating characteristic curve analysis demonstrated the ability of BTM levels to predict artery stenosis in T2DM patients.CONCLUSION BTM levels were found to be independent risk factors for severe intracranial and extracranial artery stenosis and were differentially associated with glucose and lipid metabolism in patients with T2DM.Therefore,BTMs may be promising biomarkers and potential therapeutic targets for artery stenosis.

Acinous cell AR42J-derived exosome miR125b-5p promotes acute pancreatitis exacerbation by inhibiting M2 macrophage polarization via PI3K/AKT signaling pathway

BACKGROUND The incidence rate of acute pancreatitis(AP), which is a pathophysiological process with complex etiology, is increasing globally. miR-125b-5p, a bidirectional regulatory miRNA, is speculated to exhibit anti-tumor activity. However,exosome-derived miR-125b-5p in AP has not been reported.AIM To elucidate the molecular mechanism of exosome-derived miR-125b-5p promoting AP exacerbation from the perspective of the interaction between immune cells and acinar cells.METHODS Exosomes derived from AR42J cells were isolated and extracted in active and inactive states by an exosome extraction kit, and were verified via transmission electron microscopy, nanoparticle tracking analysis, and western blotting. RNA sequencing assay technology was used to screen differentially expressed miRNAs in active and inactive AR42J cell lines, and bioinformatics analysis was used to predict downstream target genes of miR-125b-5p. The expression level of miR-125b-5p and insulin-like growth factor 2(IGF2) in the activated AR42J cell line and AP pancreatic tissue were detected by quantitative real-time polymerase chain reaction and western blots. The changes in the pancreatic inflammatory response in a rat AP model were detected by histopathological methods. Western Blot was used to detect the expression of IGF2, PI3K/AKT signaling pathway proteins, and apoptosis and necrosis related proteins.RESULTS miR-125b-5p expression was upregulated in the activated AR42J cell line and AP pancreatic tissue,while that of IGF2 was downregulated. In vitro experiments confirmed that miR-125b-5p could promote the death of activated AR42J cells by inducing cell cycle arrest and apoptosis. In addition,miR-125b-5p was found to act on macrophages to promote M1 type polarization and inhibit M2type polarization, resulting in a massive release of inflammatory factors and reactive oxygen species accumulation. Further research found that miR-125b-5p could inhibit the expression of IGF2 in the PI3K/AKT signaling pathway. Additionally, in vivo experiments revealed that miR-125b-5p can promote the progression of AP in a rat model.CONCLUSION miR-125b-5p acts on IGF2 in the PI3K/AKT signaling pathway and promotes M1 type polarization and inhibits M2 type polarization of macrophage by inhibiting IGF2 expression, resulting in a large release of pro-inflammatory factors and an inflammatory cascade amplification effect, thus aggravating AP.

Acute effect of twice-daily 15 mA transcranial alternating current stimulation on treatment-resistant depression: a case series study

Totheeditor:Major depressive disorder(MDD)is a principal cause of disability worldwide and is often associated with high morbidity and mortality rates.Although there are several therapies available for the treatment of depression,about one-third of patients with MMD will not respond to two or more antidepressant drugs with different mechanisms;the patients are then referred to as having treatment-resistant depression(TRD).Patients with TRD have a poorer quality of life,greater economic burden and increased suicidal behaviours.Therefore,new antidepressant treatments that are effective,safe,long-lasting and tolerable are needed.Ketamine infusion,intranasal esketamine and transcranial magnetic stimulation(TMS)have been used to treat early stage TRD.’A recent review suggests that electroconvulsive therapy(ECT)may be superior to ketamine for reducing depression severity in the acute treatment of TRD.

Serum Sodium Fluctuation Prediction among ICU Patients Using Neural Network Algorithm:Analysis of the MIMIC-IV Database

Sodium homeostasis disorder is one of the most common abnormal symptoms of elderly patients in intensive care unit(ICU),which may lead to physiological disorders of many organs.The current prediction of serum sodium in ICU is mainly based on the subjective judgment of doctors’experience.This study aims at this problem by studying the clinical retrospective electronic medical record data of ICU to establish a machine learning model to predict the short-term serum sodium value of ICU patients.The data set used in this study is the open-source intensive care medical information set Medical Information Mart for Intensive Care(MIMIC)-IV.The time point of serum sodium detection was selected from the ICU clinical records,and the ICU records of 25risk factors related to serum sodium were extracted from the patients within the first 12 h for statistical analysis.A prediction model of serum sodium value within 48 h was established using a feedforward neural network,and compared with previous methods.Our research results show that the neural network learning model can predict the development of serum sodium in patients using physiological indicators recorded in clinical electronic medical records within 12 h,and has better prediction effect than the serum sodium formula and other machine learning models.

Diagnostic value of preoperative examination for evaluating margin status in breast cancer

BACKGROUND A positive resection margin is a major risk factor for local breast cancer recurrence after breast-conserving surgery(BCS).Preoperative imaging examinations are frequently employed to assess the surgical margin.AIM To investigate the role and value of preoperative imaging examinations[magnetic resonance imaging(MRI),molybdenum target,and ultrasound]in evaluating margins for BCS.METHODS A retrospective study was conducted on 323 breast cancer patients who met the criteria for BCS and consented to the procedure from January 2014 to July 2021.The study gathered preoperative imaging data(MRI,ultrasound,and molybdenum target examination)and intraoperative and postoperative pathological information.Based on their BCS outcomes,patients were categorized into positive and negative margin groups.Subsequently,the patients were randomly split into a training set(226 patients,approximately 70%)and a validation set(97 patients,approximately 30%).The imaging and pathological information was analyzed and summarized using R software.Non-conditional logistic regression and LASSO regression were conducted in the validation set to identify factors that might influence the failure of BCS.A column chart was generated and applied to the validation set to examine the relationship between pathological margin range and prognosis.This study aims to identify the risk factors associated with failure in BCS.RESULTS The multivariate non-conditional logistic regression analysis demonstrated that various factors raise the risk of positive margins following BCS.These factors comprise non-mass enhancement(NME)on dynamic contrastenhanced MRI,multiple focal vascular signs around the lesion on MRI,tumor size exceeding 2 cm,type III timesignal intensity curve,indistinct margins on molybdenum target examination,unclear margins on ultrasound examination,and estrogen receptor(ER)positivity in immunohistochemistry.LASSO regression was additionally employed in this study to identify four predictive factors for the model:ER,molybdenum target tumor type(MT Xmd Shape),maximum intensity projection imaging feature,and lesion type on MRI.The model constructed with these predictive factors exhibited strong consistency with the real-world scenario in both the training set and validation set.Particularly,the outcomes of the column chart model accurately predicted the likelihood of positive margins in BCS.CONCLUSION The proposed column chart model effectively predicts the success of BCS for breast cancer.The model utilizes preoperative ultrasound,molybdenum target,MRI,and core needle biopsy pathology evaluation results,all of which align with the real-world scenario.Hence,our model can offer dependable guidance for clinical decisionmaking concerning BCS.

Comprehensive bioinformatics analysis and experimental validation:An anoikis-related gene prognostic model for targeted drug development in head and neck squamous cell carcinoma

We analyzed RNA-sequencing(RNA-seq)and clinical data from head and neck squamous cell carcinoma(HNSCC)patients in The Cancer Genome Atlas(TCGA)Genomic Data Commons(GDC)portal to investigate the prognostic value of anoikis-related genes(ARGs)in HNSCC and develop new targeted drugs.Differentially expressed ARGs were screened using bioinformatics methods;subsequently,a prognostic model including three ARGs(CDKN2A,BIRC5,and PLAU)was constructed.Our results showed that the model-based risk score was a good prognostic indicator,and the potential of the three ARGs in HNSCC prognosis was validated by the TISCH database,the model’s accuracy was validated in two independent cohorts of the Gene Expression Omnibus database.Immune correlation analysis and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno-and chemo-therapeutic responses.Potential small-molecule drugs for HNSCC were subsequently predicted using the L1000FWD database.Finally,in vitro experiments were used to verify the database findings.The relative ARG mRNA expression levels in HNSCC and surrounding normal tissues remained consistent with the model results.BIRC5 knockdown inhibited anoikis resistance in WSU-HN6 and CAL-27 cells.Molecular docking,real-time PCR,cell counting kit-8(CCK-8),plate clone,and flow cytometry analyses showed that small-molecule drugs predicted by the database may target the ARGs in the prognostic model,inhibit HNSCC cells survival rate,and promote anoikis in vitro.Therefore,we constructed a new ARG model for HNSCC patients that can predict prognosis and immune activity and identify a potential small-molecule drug for HNSCC,paving the way for clinically targeting anoikis in HNSCC.

Acute aortic dissection mimicking acute myelopathies: a case report

Myelopathy is a common etiology of acute bilateral limb weakness. While painless acute aortic dissection(AAD)is the most common catastrophic event that can mimic myelopathic manifestations of acute bilat-eral limb weakness, it is often easily ignoredWe describe a case of painless AAD in a 70-year-old man with a histo-ry of hypertension manifesting as acute myelopathy(bi-lateral limb weakness and loss of all types of sensation)with increased levels of serum myoglobin and D-dimer.Magnetic resonance imaging of the spinal cord revealed a normal thoracic and lumbar spinal cord but a dissection of the thoracic aorta. Computed tomography angiography of the chest and abdominal aorta showed a Stanford type B dissection extending throughout the thoracic aorta and into the abdominal aorta hypomere.The patient died be-cause of a sudden drop in blood pressure during transfer to vascular surgery.The clinical presentation of painless AAD mimics myelopathies.Aortic dissection should be considered in patients presenting with acute bilateral limb weakness.Physical examination of the skin temperature,dorsalis pedis artery,serum D-dimer,and myocardial markers can provide diagnostic clues.