TRIANGLE operation,combined with adequate adjuvant chemotherapy,can improve the prognosis of pancreatic head cancer:A retrospective study

BACKGROUND The TRIANGLE operation involves the removal of all tissues within the triangle bounded by the portal vein-superior mesenteric vein,celiac axis-common hepatic artery,and superior mesenteric artery to improve patient prognosis.Although previously promising in patients with locally advanced pancreatic ductal adenocarcinoma(PDAC),data are limited regarding the long-term oncological outcomes of the TRIANGLE operation among resectable PDAC patients undergoing pancreaticoduodenectomy(PD).AIM To evaluate the safety of the TRIANGLE operation during PD and the prognosis in patients with resectable PDAC.METHODS This retrospective cohort study included patients who underwent PD for pancreatic head cancer between January 2017 and April 2023,with or without the TRIANGLE operation.Patients were divided into the PD_(TRIANGLE)and PD_(non-TRIANGLE)groups.Surgical and survival outcomes were compared between the two groups.Adequate adjuvant chemotherapy was defined as adjuvant chemotherapy≥6 months.RESULTS The PD_(TRIANGLE)and PD_(non-TRIANGLE) groups included 52 and 55 patients,respectively.There were no significant differences in the baseline characteristics or perioperative indexes between the two groups.Furthermore,the recurrence rate was lower in the PD_(TRIANGLE) group than in the PD_(non-TRIANGLE) group(48.1%vs 81.8%,P<0.001),and the local recurrence rate of PDAC decreased from 37.8%to 16.0%.Multivariate Cox regression analysis revealed that PD_(TRIANGLE)(HR=0.424;95%CI:0.256-0.702;P=0.001),adequate adjuvant chemotherapy≥6 months(HR=0.370;95%CI:0.222-0.618;P<0.001)and margin status(HR=2.255;95%CI:1.252-4.064;P=0.007)were found to be independent factors for the recurrence rate.CONCLUSION The TRIANGLE operation is safe for PDAC patients undergoing PD.Moreover,it reduces the local recurrence rate of PDAC and may improve survival in patients who receive adequate adjuvant chemotherapy.

Sodium Sulfite as a Novel Hypoxia Revulsant Involved in Hypoxic Regulation in Escherichia coli

As a reducing salt,sodium sulfite could deprive oxygen in solution,which could mimic hypoxic stress in Caenorhabditis elegans.In this study,the wildtype Escherichia coli strain MG1655 was used to examine the inhibition of sodium sulfite-induced hypoxia by observing the bacterial growth curves.

Endoscopic findings of gastrointestinal involvement in Chinese patients with Behcet's disease

AIM:To report the incidence,clinical features and outcomes of gastrointestinal(GI)involvement in Behcet’s disease(BD).METHODS:A total of 168 consecutive patients with BD were screened and upper and lower GI endoscopies were performed in 148 patients.Four hundred age-and sex-matched controls were enrolled for comparison.RESULTS:Fifty-two(35.1%)patients had GI lesions.After a mean follow-up of 10 mo,ileocecal ulcers had been confirmed in 20 patients,including active ulcer(s)in 18 patients,but no ileocecal ulceration was found in controls.GI symptoms were present in 14 patients with active ulcer(s),while 4 patients with smaller ulcer were asymptomatic.Endoscopic features of ileocecalulcer were:a single ulcer(50%),larger than 1 cm in diameter(72.2%),and round/oval or volcano-type in shape(83.3%).Compared with patients without GI involvement,less ocular lesions,lower levels of albumin,erythrocyte count and hemoglobin,and higher levels of C-reactive protein and erythrocyte sedimentation rate were confirmed in the intestinal BD group.Four patients had esophageal ulcers in the BD group but no case in controls.The other endoscopic findings were similar between the two groups.The prevalence of Helicobacter pylori infection was similar in both groups.Most patients received an immunomodulator and responded well.CONCLUSION:GI lesions commonly occur in Chinese BD patients.The most frequently involved area is the ileocecal region.Esophageal ulcer might be a rare but unique lesion.

Dental pulp cell bank as a possible future source of individual hepatocytes

Mesenchymal stem cells(MSCs) as a source for regenerative medicine are now the subject of much clinical attention. There are high expectations due to their safety, low tumorigenic risk, and low ethical concerns. MSC therapy has been approved for acute graft-versus host diseases since 2015. Tooth-derived MSCs are known to have a great potential in their proliferation and differentiation capacities, even when compared with bone-marrow-derived MSCs. In particular, stem cells from human exfoliated deciduous teeth(SHEDs) are the best candidates for personal cell banking(dental pulp cell bank), because they can be obtained less invasively in the natural process of individual growth. SHEDs are known to differentiate into hepatocytes. There have been several studies showing the effectiveness of SHEDs on the treatment of liver failure in animal models. They may exert their effects either by repopulation of cells in injured liver or by paracrine mechanisms due to their immuneregulatory functions. Moreover, it may be possible to use each individuals' dental pulp cells as a future source of tailor-made differentiated hepatocytes in the context of a bioartificial liver or liver-on-a-chip to screen for drug toxicity.

Expression of HIF-1α,TGF-β1,Mucl and MMP-9 in placenta:preliminary pathophysiological study of preeclampsia

Objective:To investigate expressions of hypoxia-inducible factors-la(HIF-la),transforming growth factor-β1 (TGF-pl),mucinl(Mucl) and matrix metalloproteinase-9(MMP-9) in the placenta collected from the preeclampsia patients and normal pregnant women,so as to explore the possible pathophysiological mechanism of preeclampsia. Methods:The placenta villus tissues were obtained from 35 preeclampsia women,including 16 mild preeclampsia and 19 severe preeclampsia,and 20 normal pregnant women,within 5 minutes after placental expulsion.Expressions of HIF-1α,TGF-β1,Mucl and MMP-9 were detected by Western blot.Cellular location was observed by immunohistochemistry. Results:(1) HIF-1αwas mainly located in cytoplasm and nucleus of placental villous syncytiotrophoblast. Expression level of HIF-la in the severe preeclampsia group was significantly higher than that in the mild group or control group(P<0.01).(2) TGF-pl was located in the trophoblast cell and exuviates membrane.Expression level of TGF-pl in the severe and mild preeclampsia groups was significantly higher than that in control group (P<0.05).(3) Mucl was located in trophoblast cell and exuviates membrane.Expression level of MUC1 in the severe preeclampsia group was significantly higher than that in the mild preeclampsia group and control group(P< 0.01).(4) MMP-9 was located in the trophoblast cell and villous stroma,exuviates membrane.Expression levels of MMP-9 in the two preeclampsia groups were lower than that in control group(P>0.05). Conclusion:Expressions of HIF-lα,TGF-β1 and Mucl increased in the placenta of preeclampsia group,while MMP-9 decreased.Mucl can be induced and regulated by HIF-la and TGF-β1.Over-expression of Mucl in placenta can significantly suppress the activation of MMP-9,which may influence the infiltration of trophoblast cells.The increased expression of HIF-lαand TGF-β1 in placenta may induce higher level of Mucl.This study helped us to understand the pathophysiological mechanism of preeclampsia.

Effect of Copper Sources and Levels on Hydrogen Peroxide Generation by Mitochondria from Broiler Liver

The present experiment was performed with the objective of examining the effects of copper sources and levels on hydrogen peroxide(H_2O_2) generation by mitochondria from broiler hepatocytes. Treatments were applied to compare sources of copper(CuSO_4 versus Cu-Met) and 4 levels of dietary Cu (11,110,220 and 330 mg/kg).Day-old broilers(Cobb 500,Gallus domesticus,n=288) were randomly divided into 8 groups of 36 each and fed diets as follows:Controls(Cu 11 mg/kg) and high copper(Cu 110, 220,and 330 mg/kg),for 60 days under normal conditions.Sample collections were made at 12,36 and 60 days of age to investigate the changes in H_2O_2 generation by mitochondria from hepatocytes.Compared with those of the control diets,H_2O_2 generation by mitochondria in the high copper groups(110 to 330 mg/kg) of the two copper sources were increased(P<0.05 or P<0.01);At days 36 and 60,H_2O_2 generation by hepatic mitochondria from Cu-Met supplementation exceeded that from birds supplemented with CuSO_4 (P<0.05 or P<0.01).In addition,H_2O_2 generation by mitochondria from broilers fed with high dietary copper appeared to be associated with altered function of mitochondrial complexⅣ.The results indicated that dietary supplementation with copper induced oxidative stress damage in liver.At each level of copper supplementation,the organic Cu-Met led to more rapid H_2O_2 generation than did inorganic CuSO_4.The results also suggest that mitochondrial complexⅣmay be targeted under conditions of high dietary copper supplementation.

Low microRNA-139 expression associates with poor prognosis in patients with tumors: A meta-analysis

Background:microRNA-139(miR-139)is dysregulated in various types of tumors and plays a key role in carcinogenesis.miR-139 may be used as a diagnostic and prognostic biomarker of cancers.However,the data from the literature are not consistent.The present study aimed to verify the prognostic and diagnostic values of miR-139 in solid tumors.Data sources:PubMed,Web of Science and Embase databases were searched and publications from January 2011 to August 2017 were included.We used Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)database to further validate this meta-analysis.Results:Eight individual studies from seven articles were included.Pooled analyses showed that low miR-139 expression was related to worse overall survival(OS)[hazard ratio(HR)=2.27;95%confidence intervals(CI):1.74–2.95;P<0.001]in solid tumors,including hepatocellular carcinoma(HCC)and glioblastoma multiforme(GBM),consisting with the results of TCGA.However,our results of CRC showed that low miR-139 expression was associated with poor OS which was contradictory with the results in TCGA database and need larger samples to validate the phenomenon;whereas for CRC patients,high miR-139 expression predicted poor RFS,which was in good accordance with TCGA results.The results of 27 microarrays from GEO database showed that miR-139 expression levels were lower in tumor tissues compared to adjacent non-tumor tissues or healthy tissues.Decreased miR-139 expression was also significantly correlated with poor differentiation grade(OR=3.57;95%CI:1.44–8.85;P=0.006).However,the combined data indicated that no associations between miR-139 expression and the following parameters such as age(pooled OR=1.50;95%CI:0.69–3.24;P=0.304),gender(pooled OR=0.92;95%CI:0.56–1.51;P=0.738),tumor size(pooled OR=1.51;95%CI:0.69–3.31;P=0.298),late tumor-node-metastasis stage(pooled OR=1.63;95%CI:0.99–2.68;P=0.057)and lymph-node-metastasis(pooled OR=0.66;95%CI:0.34–1.28;P=0.222).Conclusions:Low miR-139 expression was related to poor prognosis in HCC and GBM,which could be regarded as a potential prognostic biomarker.However,its precise functional role in CRC still need to be further investigated through larger samples and multicenter studies.

Urine Flow Acceleration Is Superior to Qmax in Diagnosing BOO in Patients with BPH

Summary： We performed a retrospective, case-control study to evaluate whether the urine flow acceleration （UFA, mL/s2） is superior to maximum uroflow （Qmax, mL/s） in diagnosing bladder outlet obstruction （BOO） in patients with benign prostatic hyperplasia （BPH）. In this study, a total of 50 men with BPH （age： 58±12.5 years） and 50 controls （age： 59±13.0 years） were included. A pressure-flow study was used to determine the presence of BOO according to the recommendations of Incontinence Control Society （ICS）. The results showed that the UFA and Qmax in BPH group were much lower than those in the control group [（2.05±0.85） vs. （4.60±1.25） mL/s2 and （8.50±1.05） vs. （13.00±3.35） mL/s] （P〈0.001）. Accol;ding to the criteria （UFA〈2.05 mL/s2, Qmax〈10 mL/s）, the sensitivity and specificity of UFA vs. Qmax in diagnosing BOO were 88%, 75% vs. 81%, 63%. UFA vs. Omax, when compared with the results of P-Q chart （the kappa values in corresponding analysis）, was 0.55 vs. 0.35. The pros- tate volume, post void residual and detrusor pressure at Qmax between the two groups were 28.6±9.8 vs. 24.2±7.6 mL, 60.4±1.4 vs. 21.3±2.5 mL and 56.6±8.3 vs. 21.7±6.1 cmHzO, respectively （P〈0.05）. It was concluded that the UFA is a useful urodynamic parameter, and is superior to Qmax in diagnosing BOO in patients with BPH.

Increased CMTM4 mRNA expression predicts a poor prognosis in patients with hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is one of the most common human malignancies and main cause of cancer mortality worldwide[1].Conventional treatment for HCC consists of hepatic resection,liver transplantation and radiofrequency ablation[2,3].Despite improvements in clinical treatment,the 5-year survival rate of advanced HCC patients remains low.The exploration of novel therapeutic targets and the identification of prognostic biomarkers for HCC are vital and essential to improve clinical outcomes.CKLF-like MARVEL transmembrane domaincontaining member 4(CMTM4),mapped to chromosome 16q22.1,is the most conserved member of the CMTM family.The CMTM family comprises 9 genes:CMTM 1-8 and CKLF.Proteins from CMTM family are involved in the immune system[4],the male reproductive system[5],angiogenesis regulation,and tumorigenesis.

Chemical renal artery denervation with appropriate phenol in spontaneously hypertensive rats

Objective To explore the effectiveness of renal denervation (RDN) on blood pressure with the appropriate dosage of phenol/ethanol solution in spontaneously hypertensive rats (SHRs). Methods RDN was performed on the bilateral renal artery. Forty SHRs were divided into four groups according on the dosage of phenol (10% phenol in absolute ethanol): sham group, 0.5 mL phenol group, 1 mL phenol group and 1.5 mL phenol group (n = 10 in each group). Blood pressure was measured by tail-cuff plethysmography. Plasma creatinine was determined four weeks after the treatment. The kidneys and renal arteries were collected and processed for histological examination. Results A sustained decrease in systolic blood pressure (SBP) was only observed after the application of 1 mL phenol for four weeks, while SBP was lowered during the first week after RDN and increased in the following three weeks in the 0.5 mL and 1.5 mL phenol groups compared with the sham group. Renal norepinephrine (NE) was significantly decreased four weeks after RDN in the 1 mL and 1.5 mL phenol group compared with the sham group, but not in the 0.5 ml group. RDN with 1 mL phenol obviously reduced glomerular fibrosis. Histopathological analysis showed that tyrosine hydroxylase immunoreactivity was lower in the 1 mL and 1.5 mL phenol groups compared with the sham group. Moderate renal artery damage occurred in the 1.5 mL phenol group. Conclusion Chemical denervation with 1 ml phenol (10% phenol in absolute ethanol) effectively and safely damaged peripheral renal sympathetic nerves and contributed to the sustained reduction of blood pressure in SHRs.

Collective and Individual Assessment of the Risk of Death from COVID-19 for the Elderly,2020–2022

Introduction:Coronavirus disease 2019(COVID-19)has had profound disruptions worldwide.For a population or individual,it is critical to assess the risk of death for making preventative decisions.Methods:In this study,clinical data from approximately 100 million cases were statistically analyzed.A software and an online assessment tool were developed in Python to evaluate the risk of mortality.Results:Our analysis revealed that 76.51%of COVID-19-related fatalities occurred among individuals aged over 65 years,with frailty-associated deaths accounting for more than 80%of these cases.Furthermore,over 80%of the reported deaths involved unvaccinated individuals.A notable overlap was observed between aging and frailty-associated deaths,both of which were connected to underlying health conditions.For those with at least two comorbidities,the proportion of frailty and the proportion of COVID-19-related death were both close to 75 percent.Subsequently,we established a formula to calculate the number of deaths,which was validated using data from twenty countries and regions.Using this formula,we developed and verified an intelligent software designed to predict the death risk for a given population.To facilitate rapid risk screening on an individual level,we also introduced a six-question online assessment tool.Conclusions:This study examined the impact of underlying diseases,frailty,age,and vaccination history on COVID-19-related mortality,resulting in a sophisticated software and a user-friendly online scale to assess mortality risk.These tools offer valuable assistance in informed decision-making.

Diversification of pharmaceutical molecules via late-stage C(sp^(2))–H functionalization

C–H late-stage functionalization has gradually become a powerful approach for the rapid optimization of lead compounds’bioactivity.Significant advances in this field have been achieved in the past few years,mainly,the C–H functionalization system in(hetero)aryl C–H activation owing to the importance of(hetero)aryl moiety in pharmaceutical.In this review,we described the selected recent examples of how developed intermolecular C(sp^(2))–H functionalization methodologies involving diverse techniques diversify pharmaceutical molecules in the late stage.

Overexpressed NEDD8 as a potential therapeutic target in esophageal squamous cell carcinoma

Objective:The hyperactivated neddylation pathway plays an important role in tumorigenesis and is emerging as a promising anticancer target.We aimed to study whether NEDD8(neural precursor cell expressed,developmentally down-regulated 8)might serve as a therapeutic target in esophageal squamous cell carcinoma(ESCC).Methods:The clinical relevance of NEDD8 expression was evaluated by using The Cancer Genome Atlas(TCGA)database and tissue arrays.NEDD8-knockdown ESCC cells generated with the CRISPR/Cas9 system were used to explore the anticancer effects and mechanisms.Quantitative proteomic analysis was used to examine the variations in NEDD8 knockdown-induced biological pathways.The cell cycle and apoptosis were assessed with fluorescence activated cell sorting.A subcutaneous-transplantation mouse tumor model was established to investigate the anticancer potential of NEDD8 silencing in vivo.Results:NEDD8 was upregulated at both the mRNA and protein expression levels in ESCC,and NEDD8 overexpression was associated with poorer overall patient survival(mRNA level:P=0.028,protein level:P=0.026,log-rank test).Downregulation of NEDD8 significantly suppressed tumor growth both in vitro and in vivo.Quantitative proteomic analysis revealed that downregulation of NEDD8 induced cell cycle arrest,DNA damage,and apoptosis in ESCC cells.Mechanistic studies demonstrated that NEDD8 knockdown led to the accumulation of cullin-RING E3 ubiquitin ligases(CRLs)substrates through inactivation of CRLs,thus suppressing the malignant phenotype by inducing cell cycle arrest and apoptosis in ESCC.Rescue experiments demonstrated that the induction of apoptosis after NEDD8 silencing was attenuated by DR5 knockdown.Conclusions:Our study elucidated the anti-ESCC effects and underlying mechanisms of NEDD8 knockdown,and validated NEDD8 as a potential target for ESCC therapy.

Meditation-based Interventions Might be Helpful for Coping with the Corona Virus Disease 2019(COVID-19)

The Coronavirus Disease 2019(COVID-19)has been characterized as the first pandemic caused by a novel coronavirus and drawn intense attention in China and globally.With the incidence and mortality rates of COVID-19 rapidly growing worldwide,people have been experiencing tremendous psychological distress during the pandemic.Elevated psychological stress could compromise the human capacity to fight against COVID-19.However,effective interventions and timely mental health care to increase resilience and improve psychological wel being is still lacking,which would be the focus of this article.In this article,we briefly summarize why meditation practice may have the potential to help minimize stress-related psychological symptoms associated with the coronavirus outbreak and how we can respond efficiently and effectively to this outbreak via taking advantage of meditation.We also provide a brief introduction of a meditation program that we developed and advocate to popularize meditation practice as a viable approach to improve wellbeing while combatting COVID-19 worldwide.

Difluorocarbene-derived rapid late-stage trifluoromethylation of 5-iodotriazoles for the synthesis of^(18)F-labeled radiotracers

Difluorocarbene has emerged as a valuable intermediate to synthesize fluorides.However,difluorocarbene-derived synthesis of^(19)F/^(18)F-trifluoromethyl triazoles has not been explored.Herein,we reported the Cu(I)-promoted difluorocarbene-derived^(19)F/^(18)F-trifluoromethylation of iodotriazoles using KF/K^(18)F as the fluorine source.This approach rapidly generated a wide range of 5-trifluoromethyl-1,2,3-triazoles in good yields showing high functional group compatibility.The reaction was effective for late-stage functionalization of bioactive molecules and^(18)F-trifluoromethylation of iodotriazoles.This work provides a practical synthetic methodology for the development of triazole drugs and^(18)F-radiotracers for positron emission tomography.

Progress in the application of molecular imaging inpsychiatric disorders

Psychiatric disorders have always attracted a lot of attention from researchers due to the difficulties in their diagnoses and treatments.Molecular imaging,as an emerging technology,has played an important role in the researchers of various diseases.In recent years,molecular imaging techniques including magnetic resonance spectroscopy,nuclear medicine imaging,and fluorescence imaging have been widely used in the study of psychiatric disorders.This review will briefly summarize the progression of molecular imaging in psychiatric disorders.

Intracellular and extracellular synergistic therapy for restoring macrophage functions via anti-CD47 antibody-conjugated bifunctional nanoparticles in atherosclerosis

Atherosclerosis is a significant contributor to global cardiovascular disease.Reducing the formation of atherosclerotic plaque effectively can lead to a decrease in cardiovascular diseases.Therefore,controlling macrophage function is crucial.This study presents the creation of a bifunctional nanoparticle that is specific to macrophages to achieve intracellular and extracellular synergistic therapy for restoring macrophage functions.The nanoparticle is conjugated with anti-CD47 antibody to modulate extracellular CD47-SIRPαphagocytic signaling axis on the outer surface of macrophages and encapsulates the NLRP3 inhibitor(CY-09)to regulate intracellular inflammation response of macrophages.The results showed that the nanoparticles accumulate in the atherosclerotic plaque,alter macrophage phagocytosis,inhibit NLRP3 inflammasome activation,and decrease the plaque burden in Apoe^(-/-)mice whilst ensuring safety.Examination of single-cell RNA sequencing indicates that this multifunctional nanoparticle decreases the expression of genes linked to inflammation and manages inflammatory pathways in the plaque lesion.This study proposes a synergistic therapeutic approach that utilizes a bifunctional nanoparticle,conjugated with anti-CD47,to regulate the microenvironment of plaques.

Inflection Point Age in the Middle and Older Women—Jiangxi Province,China,2020-2022

Summary What is already known about this topic?Previous studies have predominantly examined the micro-level aspects of women aging inflection points,while macro-level research using big data on the inflection points of aging among middle-aged and elderly women in China is currently limited.

A biocompatible Horner-Wadsworth-Emmons(HWE)reaction triggered by a bioorthogonal proximity-induced platform

Here,we present a novel bioorthogonal platform that enables precise positioning of attached moieties in close proximity,thereby facilitating the discovery and optimization of biocompatible reactions.Using this platform,we achieve a Horner-Wadsworth-Emmons(HWE)reaction under physiological conditions,generating a fluorophore in situ with a yield of up to 93%.This proximity platform should facilitate the discovery of various types of biocompatible reactions,making it a versatile tool for biomedical applica-tions.

BMAL1 regulates mitochondrial fission and mitophagy through mitochondrial protein BNIP3 and is critical in the development of dilated cardiomyopathy

Dysregulation of circadian rhythms associates with cardiovascular disorders.It is known that deletion of the core circadian gene Bma/1 in mice causes dilated car-diomyopathy.However,the biological rhythm regulation system in mouse is very different from that of humans.Whether BMAL1 plays a role in regulating human heart function remains unclear.Here we generated a BMAL1 knockout human embryonic stem cell(hESC)model and further derived human BMAL1 deficient cardiomy-ocytes.We show that BMAL1 deficient hESC-derived cardiomyocytes exhibited typical phenotypes of dilated cardiomyopathy including attenuated contractility,cal-cium dysregulation,and disorganized myofilaments.In addition,mitochondrial fission and mitophagy were suppressed in BMAL1 deficient hESC-cardiomyocytes,which resulted in significantly attenuated mitochondrial oxidative phosphorylation and compromised cardiomy-ocyte function.We also found that BMAL1 binds to the E-box element in the promoter region of BNIP3 gene and specifically controls BNIP3 protein expression.BMAL1 knockout directly reduced BNIP3 protein level,causing compromised mitophagy and mitochondria dysfunction and thereby leading to compromised cardiomyocyte function.Our data indicated that the core circadian gene S/VMLf is critical for normal mitochondria activities and cardiac function.Circadian rhythm disruption may directly link to compromised heart function and dilated cardiomyopathy in humans.