Impact of frailty on short-term postoperative outcomes in patients undergoing colorectal cancer surgery:A systematic review and meta-analysis

BACKGROUND Colorectal cancer is a major global health challenge that predominantly affects older people.Surgical management,despite advancements,requires careful consideration of preoperative patient status for optimal outcomes.AIM To summarize existing evidence on the association of frailty with short-term postoperative outcomes in patients undergoing colorectal cancer surgery.METHODS A literature search was conducted using PubMed,EMBASE and Scopus databases for observational studies in adult patients aged≥18 years undergoing planned or elective colorectal surgery for primary carcinoma and/or secondary metastasis.Only studies that conducted frailty assessment using recognized frailty assess-ment tools and had a comparator group,comprising nonfrail patients,were included.Pooled effect sizes were reported as weighted mean difference or relative risk(RR)with 95%confidence intervals(CIs).RESULTS A total of 24 studies were included.Compared with nonfrail patients,frailty was associated with an increased risk of mortality at 30 d(RR:1.99,95%CI:1.47-2.69),at 90 d(RR:4.76,95%CI:1.56-14.6)and at 1 year(RR:5.73,95%CI:2.74-12.0)of follow up.Frail patients had an increased risk of any complications(RR:1.81,95%CI:1.57-2.10)as well as major complications(Clavien-Dindo classification grade≥III)(RR:2.87,95%CI:1.65-4.99)compared with the control group.The risk of reoperation(RR:1.18,95%CI:1.07-1.31),readmission(RR:1.70,95%CI:1.36-2.12),need for blood transfusion(RR:1.67,95%CI:1.52-1.85),wound complications(RR:1.49,95%CI:1.11-1.99),delirium(RR:4.60,95%CI:2.31-9.16),risk of prolonged hospitalization(RR:2.09,95%CI:1.22-3.60)and discharge to a skilled nursing facility or rehabilitation center(RR:3.19,95%CI:2.0-5.08)was all higher in frail patients.CONCLUSION Frailty in colorectal cancer surgery patients was associated with more complications,longer hospital stays,higher reoperation risk,and increased mortality.Integrating frailty assessment appears crucial for tailored surgical management.

New Interpretation of Neonatal Outcomes by Phenotypically Classified Preterm Syndrome:A Retrospective Cohort Study

Objective:The global aim to lower preterm birth rates has been hampered by the insufficient and incomplete understanding of its etiology,classification,and diagnosis.This study was designed to evaluate the association of phenotypically classified preterm syndromes with neonatal outcomes;to what extent would these outcomes be modified after the obstetric interventions,including use of glucocorticoid,magnesium sulfate,and progesterone.Methods:This was a retrospective cohort study conducted at Tongji Hospital(composed of Main Branch,Optical Valley Branch and Sino-French New City Branch)in Wuhan.A total of 900 pregnant women and 1064 neonates were retrospectively enrolled.The outcomes were the distribution of different phenotypes among parturition signs and pathway to delivery,the association of phenotypically classified clusters with short-term unfavorable neonatal outcomes,and to what extent these outcomes could be modified by obstetric interventions.Results:Eight clusters were identified using two-step cluster analysis,including premature rupture of fetal membranes(PPROM)phenotype,abnormal amniotic fluid(AF)phenotype,placenta previa phenotype,mixed condition phenotype,fetal distress phenotype,preeclampsia-eclampsia&hemolysis,elevated liver enzymes,and low platelets syndrome(PE-E&HELLP)phenotype,multiple fetus phenotype,and no main condition phenotype.Except for no main condition phenotype,the other phenotypes were associated with one or more complications,which conforms to the clinical practice.Compared with no main condition phenotype,some phenotypes were significantly associated with short-term adverse neonatal outcomes.Abnormal AF phenotype,mixed condition phenotype,PE-E&HELLP phenotype,and multiple fetus phenotype were risk factors for neonatal small-for gestation age(SGA);placenta previa phenotype was not associated with adverse outcomes except low APGAR score being 0-7 at one min;mixed condition phenotype was associated with low APGAR scores,SGA,mechanical ventilation,and gradeⅢ-Ⅳintraventricular hemorrhage(IVH);fetal distress phenotype was frequently associated with neonatal SGA and mechanical ventilation;PE-E&HELLP phenotype was correlated with low APGAR score being 0-7 at one min,SGA and neonatal intensive care unit(NICU)admission;multiple fetus phenotype was not a risk factor for the outcomes included except for SGA.Not all neonates benefited from obstetric interventions included in this study.Conclusion:Our research disclosed the independent risk of different preterm phenotypes for adverse pregnancy outcomes.This study is devoted to putting forward the paradigm of classifying preterm birth phenotypically,with the ultimate purpose of defining preterm phenotypes based on multi-center studies and diving into the underlying mechanisms.

Establishment of a Rat Model of Capillary Leakage Syndrome Induced by Cardiopulmonary Resuscitation After Cardiac Arrest

Objective:Cardiopulmonary resuscitation(CPR)after cardiac arrest(CA)is one of the main causes of capillary leakage syndrome(CLS).This study aimed to establish a stable CLS model following the CA and cardiopulmonary resuscitation(CA-CPR)model in Sprague-Dawley(SD)rats.Methods:We conducted a prospective,randomized,animal model study.All adult male SD rats were randomly divided into a normal group(group N),a sham operation group(group S),and a cardiopulmonary resuscitation group(group T).The SD rats of the three groups were all inserted with 24-G needles through their left femoral arteries and right femoral veins.In group S and group T,the endotracheal tube was intubated.In group T,CA induced by asphyxia(AACA)was caused by vecuronium bromide with the endotracheal tube obstructed for 8 min,and the rats were resuscitated with manual chest compression and mechanical ventilation.Preresuscitation and postresuscitation measurements,including basic vital signs(BVS),blood gas analysis(BG),routine complete blood count(CBC),wet-to-dry ratio of tissues(W/D),and the HE staining results after 6 h were evaluated.Results:In group T,the success rate of the CA-CPR model was 60%(18/30),and CLS occurred in 26.6%(8/30)of the rats.There were no significant differences in the baseline characteristics,including BVS,BG,and CBC,among the three groups(P>0.05).Compared with pre-asphyxia,there were significant differences in BVS,CBC,and BG,including temperature,oxygen saturation(SpO_(2)),mean arterial pressure(MAP),central venous pressure(CVP),white blood cell count(WBC),hemoglobin,hematocrit,pH,pCO_(2),pO_(2),SO_(2),lactate(Lac),base excess(BE),and Na+(P<0.05)after the return of spontaneous circulation(ROSC)in group T.At 6 h after ROSC in group T and at 6 h after surgery in groups N and S,there were significant differences in temperature,heart rate(HR),respiratory rate(RR),SpO_(2),MAP,CVP,WBC,pH,pCO_(2),Na+,and K+among the three groups(P<0.05).Compared with the other two groups,the rats in group T showed a significantly increased W/D weight ratio(P<0.05).The HE-stained sections showed consistent severe lesions in the lung,small intestine,and brain tissues of the rats at 6 h after ROSC following AACA.Conclusion:The CA-CPR model in SD rats induced by asphyxia could reproduce CLS with good stability and reproducibility.

Integrative analysis of aberrant Wnt signaling in hepatitis B virus-related hepatocellular carcinoma

AIM: To comprehensively understand the underlying molecular events accounting for aberrant Wnt signaling activation in hepatocellular carcinoma(HCC).METHODS: This study was retrospective. The HCC tissue specimens used in this research were obtained from patients who underwent liver surgery. The Catalogue of Somatic Mutations in Cancer(COSMIC) database was searched for the mutation statuses of CTNNB1, TP53, and protein degradation regulator genes of CTNNB1. Dual-luciferase reporter assay was performed with TOP/FOP reporters to detect whether TP53 gain-of-function(GOF) mutations could enhance the transcriptional activity of Wnt signaling. Methylation sensitive restriction enzyme-quantitative PCR was used to explore the methylation status of Cp G islands located in the promoters of APC, SFRP1, and SFRP5 in HCCs with different risk factors. Finally, nestedreverse transcription PCR was performed to examine the integration of HBx in front of LINE1 element and the existence of HBx-LINE1 chimeric transcript in Hepatitis B virus-related HCC. All results in this article were analyzed with the software SPSS version 19.0 for Windows, and different groups were compared by χ2 test as appropriate.RESULTS: Based on the data from COSMIC database, compared with other solid tumors, mutation frequency of CTNNB1 was significantly higher in HCC(P < 0.01). The rate of CTNNB1 mutation was significantly less frequent in Hepatitis B virus-related HCC than in other etiologies(P < 0.01). Dual-luciferase reporter system and TOP/FOP reporter assays confirmed that TP53 GOF mutants were able to enhance the transcriptional ability of Wnt signaling. An exclusive relationship between the status of TP53 and CTNNB1 mutations was observed. However, according to the COSMIC database, TP53 GOF mutation is rare in HCC, which indicates that TP53 GOF mutation is not a reason for the aberrant activation of Wnt signaling in HCC. APC and AXIN1 were mutated in HCC. By using methylation sensitive restriction enzyme-quantitative PCR, hypermethylation of APC was detected in HCC with different risk factors, whereas SFRP1 and SFRP5 were not hypermethylated in any of the HCC etiologies, which indicates thatthe mutation of APC and AXIN1, together with the methylation of APC could take part in the overactivation of Wnt signaling. Nested-reverse transcription PCR failed to detect the integration of HBx before the LINE1 element, or the existence of an HBx-LINE1 chimeric transcript, suggesting that integration could not play a role in the aberrant activation of Wnt signaling in HCC.CONCLUSION: In HCC, genetic/epigenetic aberration of CTNNB1 and its protein degradation regulators are the major cause of Wnt signaling overactivation.

Antiviral therapies for hepatitis B virus-related hepatocellular carcinoma

Chronic hepatitis B virus(HBV) infection is a critical risk factor for the carcinogenesis and progression of hepatocellular carcinoma(HCC). It promotes HCC development by inducing liver fibrogenesis, genetic and epigenetic alterations, and the expression of active viral-coded proteins. Effective antiviral treatments inhibit the replication of HBV, reduce serum viral load and accelerate hepatitis B e antigen serum conversion. Timely initiation of antiviral treatment is not only essential for preventing the incidence of HCC in chronic hepatitis B patients, but also important for reducing HBV reactivation, improving liver function, reducing or delaying HCC recurrence, and prolonging overall survival of HBV-related HCC patients after curative and palliative therapies. The selection of antiviral drugs, monitoring of indicators such as HBV DNA and hepatitis B surface antigen, and timely rescue treatment when necessary, are essential in antiviral therapies for HBVrelated HCC.

Radix Ilicis Pubescentis total flavonoids ameliorates neuronal damage and reduces lesion extent in a mouse model of transient ischemic attack

Flavonoids are a major component in the traditional Chinese medicine Radix Ilicis Pubescentis.Previous studies have shown that the administration of Radix Ilicis Pubescentis total flavonoids is protective in cerebral ischemia.However,to our knowledge,no studies have examined whether the total flavonoids extracted from Radix Ilicis Pubescentis prevent or ameliorate neuronal damage following transient ischemic attacks.Therefore,Radix Ilicis Pubescentis total flavonoids question and the potential underlying mechanisms.Thus,beginning 3 days before the induction of a mouse model of transient ischemic attack using tert-butyl hydroperoxide injections,mice were intragastrically administered 0.3,0.15,or 0.075 g/kg of Radix Ilicis Pubescentis total flavonoids daily for 10 days.The results of spectrophotometric analyses demonstrated that Radix Ilicis Pubescentis total flavonoids enhanced oxygen free radical scavenging and reduced pathological alterations in the brain.Hematoxylin-eosin staining results showed that Radix Ilicis Pubescentis total flavonoids reduced hippocampal neuronal damage and cerebral vascular injury in this mouse model of transient ischemic attack.These results suggest that the antioxidant effects of Radix Ilicis Pubescentis total flavonoids alleviate the damage to brain tissue caused by transient ischemic attack.

SERS activity of carbon nanotubes modified by silver nanoparticles with different particle sizes

A two-dimensional(2D)surface-enhanced Raman scattering(SERS)substrate is fabricated by decorating carbon nanotube(CNT)films with Ag nanoparticles(Ag NPs)in different sizes,via simple and low-cost chemical reduction method and self-assembling method.The change of Raman and SERS activity of carbon nanotubes/Ag nanoparticles(CNTs/Ag NPs)composites with varying size of Ag NPs are investigated by using rhodamine 6G(R6G)as a probe molecule.Meanwhile,the scattering cross section of Ag NPs and the distribution of electric field of CNTs/Ag NPs composite are simulated through finite difference time domain(FDTD)method.Surface plasmon resonance(SPR)wavelength is redshifted as the size of Ag NPs increases,and the intensity of SERS and electric field increase with Ag NPs size increasing.The experiment and simulation results show a Raman scattering enhancement factor(EF)of 108for the hybrid substrate.

电针预处理对心肌缺血再灌注大鼠线粒体能量代谢的影响

Objective:To explore the effects of electroacupuncture pretreatment on mitochondrial energy metabolism in the rats with myocardial ischemia reperfusion injury(MIRI).Methods:A total of 60 SPF Wistar rats were randomly divided into a sham-operation group(sham group),a myocardial ischemia reperfusion injury group(MIRI group)and an electroacupuncture pretreatment group(EA group),20 rats in each one.The rats in the sham group and the MIRI group were binded for 7 days,once a day,20 min each time.On the 8th day,the sample was collected after the heart exposed for 50 min in thoractomy in the sham group and the sample was collected after ischemia for 20 min and reperfusion for 30 min in thoractomy in the MIRI group.In the EA group,the pretreatment intervention with electroacupuncture was applied at"Neiguan(内关PC6)","Guanyuan(关元CV4)"and"Zusanli(足三里ST36)"in the rats for 7 days,once a day,20 min each time.On the 8th day,after ischemia for 20 min and reperfusion for 30 min in thoractomy,the sample was collected in the EA group.The changes in STⅡsegment of electroacardiogram(ECG)were observed and measured.Using enzymelinked immunosorbent assay(ELISA),the concentrations of cardiac troponin T(cTnT)and cardiac troponin I(cTnl)were detected.Using nitro blue tetrazolium chloride monohydrate(NBT)staining,the myocardial infarction weight percentage was measured.Using ELISA,the concentrations of mitochondrial adenosine monophosphate(AMP),adenosine diphosphate(ADP)and adenosine triphosphate(ATP)were detected.Results:(1)STⅡchanges:in 20 min of ligation,compared with the sham group,the STⅡsegment of electrocardiograph(ECG)was elevated significantly in the MIRI group and EA group(both P<0.01),but the elevation range in the EA group was lower than that of the MIRI group(P<0.01).After reperfusion for30 min,the STⅡsegment was fallen by over 50%in the MIRI group and the EA group.Simultaneously,the STⅡsegment in the EA group was lower than that of the MIRI group(P<0.01).(2)Regarding myocardial infarction weight percentage,compared with the sham group,the infarction weight was larger in the MIRI group and the EA group(both P<0.05)and the infarction weight in the EA group was lower than that of the MIRI group(P<0.05).(3)Regarding the levels of serum cTnt and cTnI,compared with the sham group,the levels of serum cTnT and cTnI were higher in the MIRI group and the EA group(all P<0.01)and the levels of cTnT and cTnI in the EA group were lower than that of the MIRI group(both P<0.01).(4)Regarding the concentrations of AMP,ADP and ATP,compared with the sham group,ATP concentration was lower in the MIRI group and the EA group(both P<0.01)and the concentrations of AMP and ADP were higher(P<0.05,P<0.01).Compared with the MIRI group,ATP concentration was higher in the EA group(P<0.05)and the concentrations of AMP and ADP were lower(both P<0.01).Conclusions:Electroacupuncture pretreatment reduces the elevation of ECG STⅡsegment,decreases the concentrations of myocardial injury markers,cTnT and cTnI and regulates the transfer among AMP,ATP and ADP.The protective effect of electroacupuncture pretreatment may result from the regulation of mitochondrial energy metabolism.

AtECB1/MRL7, a Thioredoxin-Like Fold Protein with Disulfide Reductase Activity, Regulates Chloroplast Gene Expression and Chloroplast Biogenesis in Arabidopsis thaliana

Plastid-encoded RNA polymerase （PEP） is closely associated with numerous factors to form PEP complex for plastid gene expression and chloroplast development. However, it is not clear how PEP complex are regulated in chloroplast. Here, one thioredoxin-like fold protein, Arabidopsis early chloroplast biogenesis 1 （AtECB1）, an allele of MRL7, was identified to regulate PEP function and chloroplast biogenesis. The knockout lines for AtECB1 displayed albino phenotype and impaired chloroplast development. The transcripts of PEP-dependent plastid genes were barely detected, suggesting that the PEP activity is almost lost in atecbl-1. Although AtECB1 was not identified in PEP complex, a yeast two-hybrid assay and pull-down experiments demonstrated that it can interact with Trx Z and FSD3, two intrinsic subunits of PEP complex, respectively. This indicates that AtECB1 may play a regulatory role for PEP-dependent plastid gene expression through these two subunits. AtECB1 contains a βαβαββα structure in the thioredoxin-like fold domain and lacks the typical C-X-X-C active site motif. Insulin assay demonstrated that AtECB1 harbors disulfide reductase activity in vitro using the purified recombinant AtECB1 protein. This showed that this thioredoxin-like fold protein, AtECB1 also has the thioredoxin activity. AtECB1 may play a role in thioredoxin signaling to regulate plastid gene expression and chloroplast development.

Optimized cutoff maternal age for adverse obstetrical outcomes: a multicenter retrospective cohort study in Urban China during 2011 to 2012

Background:China’s two-child policy has led to a trend of aging in pregnancy which was associated with adverse outcomes.This study aimed to identify the clinically cutoff maternal age for adverse obstetric outcomes in China.Methods:This secondary analysis of a multicenter retrospective cohort study included data of childbearing women from 39 hospitals collected in urban China during 2011 to 2012.Logistic regression was used to assess the adjusted odds ratios(aOR)of adverse outcomes in different age groups in comparison to women aged 20 to 24 years.The adjustments included the location of the hospital,educational level,and residence status.Clinically cutoff age was defined as the age above which the aOR continuously become both statistically(P<0.05)and clinically(aOR>2)significant.Results:Overall,108,059 women were recruited.In primiparae,clinically cutoff maternal ages for gestational diabetes(aOR:2.136,95%confidence interval[CI]:1.856-2.458,P<0.001),placenta previa(aOR:2.400,95%CI:1.863-3.090,P<0.001),cesarean section(aOR:2.511,95%CI:2.341-2.694,P<0.001),hypertensive disorder(aOR:2.122,95%CI:1.753-2.569,P<0.001),post-partum hemorrhage(aOR:2.129,95%CI:1.334-3.397,P<0.001),and low birth weight(aOR:2.174,95%CI:1.615-2.927,P<0.001)were 27,31,33,37,41,and 41 years,respectively.In multiparae,clinically cutoff ages for gestational diabetes(aOR:2.977,95%CI:1.808-4.904,P<0.001),hypertensive disorder(aOR:2.555,95%CI:1.836-3.554,P<0.001),cesarean section(aOR:2.224,95%CI:1.952-2.534,P<0.001),post-partum hemorrhage(aOR:2.140,95%CI:1.472-3.110,P<0.001),placenta previa(aOR:2.272,95%CI:1.375-3.756,P<0.001),macrosomia(aOR:2.215,95%CI:1.552-3.161,P<0.001),and neonatal asphyxia(aOR:2.132,95%CI:1.461-3.110,P<0.001)were 29,31,33,35,35,41,and 41 years,respectively.Conclusions:Early cutoff ages for gestational diabetes and cesarean section highlight a reasonable childbearing age in urban China.The various optimized cutoff ages for different adverse pregnancy outcomes should be carefully considered in childbearing women.

A Novel Case of Pulmonary Nocardiosis with Secondary Hemophagocytic Lymphohistiocytosis

Pulmonary nocardiosis is an opportunistic infection,especially in immunocompromised patients.Hemophagocytic lymphohistiocytosis （HLH） is a rare but potentially fatal disease.We report a case of pulmonary nocardiosis with secondary HLH.

Comparative study of coherent terahertz emission from Fe/Pt ferromagnetic heterostructures

The ultrafast spin dynamic of in-plane magnetized Fe/Pt films was investigated by terahertz emission spectroscopy. The amplitude of the emitted terahertz wave is proportional to the intensity of the exciting laser beams.Both the amplitude and polarity of the terahertz wave can be adjusted by modifying the external magnetic field.The dependency of the amplitude on external magnetic fields is coincident to the hysteresis loops of the sample.Also, the polarity of the terahertz wave is reversed, as the magnetization orientation is reversed. The superdiffusive transient spin current with an inverse spin Hall effect is attributed to the main mechanism of the terahertz emission.