Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

CNKSR2 interactome analysis indicates its association with the centrosome/microtubule system

The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.

SLC26A4 gene polymorphism and late-onset Alzheimer’s disease in a Han Chinese population from Qingdao,China

In a recent genome-wide association study, the SLC26A4 gene rs2072064 polymorphism was found to be associated with late-onset Alzheimer＇s disease in Caucasians. Here, we investigated this association in a large Northern Han Chinese cohort consisting of 599 sporadic late-onset Alzheimer＇s disease patients and 598 healthy controls matched for sex and age in a Northern Han Chinese population from Qingdao, China. Genotyping by the polymerase chain reaction-ligase detection reaction revealed that there were significant differences in the genotype （P = 0.017） and allele （P = 0.007） frequencies of the rs2072064 polymorphism between late-onset Alzheimer＇s disease patients and controls. The A allele of this polymorphism was significantly associated with a reduced risk of late-onset Alzheimer＇s disease （odds ratio （OR） = 0.792, 95% confidence interval （CI） = 0.670-0.937, P = 0.007）. When the data were stratified by the apolipoprotein E E4 status, there was a significant difference only among apolipoprotein E E4 non-carriers （genotypic P = 0.001, allelic P = 0.001）. Furthermore, the association between rs2072064 and late-onset Alzheimer＇s disease remained significant by logistic regression analysis after adjustment for age, gender, and the apolipoprotein E E4 carrier status （dominant model： OR = 0.787, 95% CI = 0.619-1.000, P = 0.050; recessive model： OR = 0.655, 95% CI = 0.448-0.959, P= 0.030; additive model： OR = 0.792, 95% CI = 0.661-0.950, P = 0.012）. These findings suggest that SLC26A4 is a susceptibility gene for late-onset Alzheimer＇s disease in a Northern Han Chinese population from the Qingdao area.

The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury

We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.

Kelp Fucoidans Facilitate Vascular Recanalization via Inhibiting Excessive Activation of Platelet in Deep Venous Thrombosis Model of Mouse

This study was carried out explore the mechanism underlying the inhibition of platelet activation by kelp fucoidans in deep venous thrombosis(DVT)mouse.In the control and sham mice,the walls of deep vein were regular and smooth with intact intima,myometrium and adventitia.The blood vessel was wrapped with the tissue and there was no thrombosis in the lumen.In the DVT model,the wall was uneven with thicken intima,myometrium and adventitia.After treated with fucoidans LF1 and LF2,the thrombus was dissolved and the blood vessel was recanalized.Compared with the control group,the ROS content,ET-1 and VWF content and the expression of PKC-βand NF-κB in the model were significantly higher(P<0.05);these levels were significantly reduced following treatments with LF2 and LF1.Compared with H_(2)O_(2)treated-HUVECs,combined LF1 and LF2 treatment resulted in significant decrease in the expression of PKC-β,NF-κB,VWF and TM protein(P<0.05).It is clear that LF1 and LF2 reduces DVT-induced ET-1,VWF and TM expressions and production of ROS,thus inhibiting the activation of PKC-β/NF-κB signal pathway and the activation of coagulation system and ultimately reducing the formation of venous thrombus.

Association of complement components with risk of colorectal cancer:A systematic review and meta-analysis

BACKGROUND Complement components could contribute to the tumor microenvironment and the systemic immune response.Nevertheless,their role in colorectal cancer(CRC)remains a contentious subject.AIM To elucidate the relationship between complement components and CRC risk and clinical characteristics.METHODS Searches were conducted in PubMed,the Cochrane Library,and the China National Knowledge Infrastructure database until June 1,2023.We included cohort studies encompassing participants aged≥18 years,investigating the association between complement components and CRC.The studies were of moderate quality or above,as determined by the Agency for Healthcare Research and Quality.The meta-analysis employed fixed-effects or random-effects models based on the I^(2)test,utilizing risk ratio(RR)and their corresponding 95%confidence interval(CI)for outcomes.Sensitivity and subgroup analyses were performed to validate the robustness of the collective estimates and identify the source of heterogeneity.RESULTS Data from 15 studies,comprising 1631 participants that met the inclusion criteria,were included in the meta-analysis.Our findings indicated that protein levels of cluster of differentiation 46(CD46)(RR=3.66,95%CI:1.75-7.64,P<0.001),CD59(RR=2.86,95%CI:1.36-6.01,P=0.005),and component 1(C1)(RR=5.88,95%CI:1.75-19.73,P=0.004)and serum levels of C3(standardized mean difference=1.82,95%CI:0.06-3.58,P=0.040)were significantly elevated in patients with CRC compared to healthy controls.Strong expression of CD55 or CD59 was associated with a higher incidence of lymph node metastasis,whereas strong CD46 expression correlated with a higher incidence of tumor differentiation compared to low CD46 expression(P<0.05 for all).Although specific pooled results demonstrated notable heterogeneity,subgroup analyses pointed to regional differences as the primary source of inconsistency among the studies.CONCLUSION Our analysis underscores that increased levels of specific complement components are associated with a heightened risk of CRC,emphasizing the potential significance of monitoring elevated complement component levels.

Special electromyographic features in a child with paramyotonia congenita: A case report and review of literature

BACKGROUND Paramyotonia congenita(PMC)stands as a rare sodium channelopaty of skeletal muscle,initially identified by Eulenburg.The identification of PMC often relies on electromyography(EMG),a diagnostic technique.The child’s needle EMG unveiled trains of myotonic discharges with notably giant amplitudes,alongside irregular wave trains of myotonic discharges.This distinctive observation had not surfaced in earlier studies.CASE SUMMARY We report the case of a 3-year-old female child with PMC,who exhibited la-ryngeal stridor,muffled speech,myotonia from birth.Cold,exposure to cool water,crying,and physical activity exacerbated the myotonia,which was relieved in warmth,yet never normalized.Percussion myotonia was observable in bilateral biceps.Myotonia symptoms remained unchanged after potassium-rich food consumption like bananas.Hyperkalemic periodic paralysis was excluded.Cranial magnetic resonance imaging yielded normal results.Blood potassium remained within normal range,while creatine kinase showed slight elevation.Exome-wide genetic testing pinpointed a heterozygous mutation on chromosome SCN4A:c.3917G>A(p.G1306E).After a six-month mexiletine regimen,symptoms alleviated.CONCLUSION In this case revealed the two types of myotonic discharges,and had not been documented in other studies.We underscore two distinctive features:Giant-amplitude potentials and irregular waves.

TIPE2 is Essential for Apocynin-mediated Protection against Intestinal Ischemia/Reperfusion-induced Acute Lung Injury

Intestinal ischemia/reperfusion(II/R)is a severe clinical circumstance which is frequently apparent in situations including midgut volvulus,superior mesenteric vessels closure and hemorrhagic shock.II/R not only brings about severe intestinal local damage but also leads to remote organs injury including lung,liver etc[1].Lung injury is the most common and severe complications which manifested as pulmonary susceptibility,respiratory dysfunction,and even acute respiratory distress syndrome(ARDS)[2].

Facile Surface Engineering of NiCo_(2)O_(4) to Boost Propane Oxidation Activity

Spinel oxide(NiCo_(2)O_(4))has demonstrated great potential to replace noble metal catalysts for the oxidation reaction of air pollutants.To further boost the oxidation ability of such catalysts,in this study,a facile surface-engineering strategy wherein NiCo_(2)O_(4) was treated with different alkali solvents was developed.The obtained catalyst(NiCo_(2)O_(4)-OH)showed a higher surface alkalinity and more surface defects compared to the pristine spinel oxide,including enhanced structural distortion as well as promoted oxygen vacancies.The propane oxidation ability of NiCo_(2)O_(4)-OH was greatly enhanced,with a propane conversion rate that was approximately 6.4 times higher than that of pristine NiCo_(2)O_(4) at a reaction temperature 193℃.This work sets a valuable paradigm for the surface modulation of spinel oxide via alkali treatment to ensure a high-performance oxidation catalyst.

Clinical efficacy and safety of double-channel anastomosis and tubular gastroesophageal anastomosis in gastrectomy

BACKGROUND With the continuous progress of surgical technology and improvements in medical standards,the treatment of gastric cancer surgery is also evolving.Proximal gastrectomy is a common treatment,but double-channel anastomosis and tubular gastroesophageal anastomosis have attracted much attention in terms of surgical options.Each of these two surgical methods has advantages and disadvantages,so it is particularly important to compare and analyze their clinical efficacy and safety.AIM To compare the surgical safety,clinical efficacy,and safety of double-channel anastomosis and tubular gastroesophageal anastomosis in proximal gastrectomy.METHODS The clinical and follow-up data of 99 patients with proximal gastric cancer who underwent proximal gastrectomy and were admitted to our hospital between January 2018 and September 2023 were included in this retrospective cohort study.According to the different anastomosis methods used,the patients were divided into a double-channel anastomosis group(50 patients)and a tubular gastroesophageal anastomosis group(49 patients).In the double-channel anastomosis,Roux-en-Y anastomosis of the esophagus and jejunum was performed after proximal gastric dissection,and then side-to-side anastomosis was performed between the residual stomach and jejunum to establish an antireflux barrier and reduce postoperative gastroesophageal reflux.In the tubular gastroesophageal anastomosis group,after the proximal end of the stomach was cut,tubular gastroplasty was performed on the distal stump of the stomach and a linear stapler was used to anastomose the posterior wall of the esophagus and the anterior wall of the stomach tube.The main outcome measure was quality of life 1 year after surgery in both groups,and the evaluation criteria were based on the postgastrectomy syndrome assessment scale.The greater the changes in body mass,food intake per meal,meal quality subscale score,and total measures of physical and mental health score,the better the condition;the greater the other indicators,the worse the condition.The secondary outcome measures were intraoperative and postoperative conditions,the incidence of postoperative long-term complications,and changes in nutritional status at 1,3,6,and 12 months after surgery.RESULTS In the double-channel anastomosis cohort,there were 35 males(70%)and 15 females(30%),33(66.0%)were under 65 years of age,and 37(74.0%)had a body mass index ranging from 18 to 25 kg/m2.In the group undergoing tubular gastroesophageal anastomosis,there were eight females(16.3%),21(42.9%)individuals were under the age of 65 years,and 34(69.4%)had a body mass index ranging from 18 to 25 kg/m2.The baseline data did not significantly differ between the two groups(P>0.05 for all),with the exception of age(P=0.021).The duration of hospitalization,number of lymph nodes dissected,intraoperative blood loss,and perioperative complication rate did not differ significantly between the two groups(P>0.05 for all).Patients in the dual-channel anastomosis group scored better on quality of life measures than did those in the tubular gastroesophageal anastomosis group.Specifically,they had lower scores for esophageal reflux[2.8(2.3,4.0)vs 4.8(3.8,5.0),Z=3.489,P<0.001],eating discomfort[2.7(1.7,3.0)vs 3.3(2.7,4.0),Z=3.393,P=0.001],total symptoms[2.3(1.7,2.7)vs 2.5(2.2,2.9),Z=2.243,P=0.025],and other aspects of quality of life.The postoperative symptoms[2.0(1.0,3.0)vs 2.0(2.0,3.0),Z=2.127,P=0.033],meals[2.0(1.0,2.0)vs 2.0(2.0,3.0),Z=3.976,P<0.001],work[1.0(1.0,2.0)vs 2.0(1.0,2.0),Z=2.279,P=0.023],and daily life[1.7(1.3,2.0)vs 2.0(2.0,2.3),Z=3.950,P<0.001]were all better than those of the tubular gastroesophageal anastomosis group.The group that underwent tubular gastroesophageal anastomosis had a superior anal exhaust score[3.0(2.0,4.0)vs 3.5(2.0,5.0),Z=2.345,P=0.019]compared to the dual-channel anastomosis group.Hemoglobin,serum albumin,total serum protein,and the rate at which body mass decreased one year following surgery did not differ significantly between the two groups(P>0.05 for all).CONCLUSION The safety of double-channel anastomosis in proximal gastric cancer surgery is equivalent to that of tubular gastric surgery.Compared with tubular gastric surgery,double-channel anastomosis is a preferred surgical technique for proximal gastric cancer.It offers advantages such as less esophageal reflux and improved quality of life.

Diagnostic and prognostic role of LINC01767 in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is a primary contributor to cancer-related mortality on a global scale.However,the underlying molecular mechanisms are still poorly understood.Long noncoding RNAs are emerging markers for HCC diagnosis,prognosis,and therapeutic target.No study of LINC01767 in HCC was published.AIM To conduct a multi-omics analysis to explore the roles of LINC01767 in HCC for the first time.METHODS DESeq2 Package was used to analyze different gene expressions.Receiver operating characteristic curves assessed the diagnostic performance.Kaplan-Meier univariate and Cox multivariate analyses were used to perform survival analysis.The least absolute shrinkage and selection operator(LASSO)-Cox was used to identify the prediction model.Subsequent to the validation of LINC01767 expression in HCC fresh frozen tissues through quantitative real time polymerase chain reaction,next generation sequencing was performed following LINC01767 over expression(GSE243371),and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes/Gene Set Enrichment Analysis/ingenuity pathway analysis was carried out.In vitro experiment in Huh7 cell was carried out.RESULTS LINC01767 was down-regulated in HCC with a log fold change=1.575 and was positively correlated with the cancer stemness.LINC01767 was a good diagnostic marker with area under the curve(AUC)[0.801,95% confidence interval(CI):0.751-0.852,P=0.0106]and an independent predictor for overall survival(OS)with hazard ratio=1.899(95%CI:1.01-3.58,P=0.048).LINC01767 nomogram model showed a satisfied performance.The top-ranked regulatory network analysis of LINC01767 showed the regulation of genes participating various pathways.LASSO regression identified the 9-genes model showing a more satisfied performance than 5-genes model to predict the OS with AUC>0.75.LINC01767 was down-expressed obviously in tumor than para-tumor tissues in our cohort as well as in cancer cell line;the over expression of LINC01767 inhibit cell proliferation and clone formation of Huh7 in vitro.CONCLUSION LINC01767 was an important tumor suppressor gene in HCC with good diagnostic and prognostic performance.

Analysis of lymph node metastasis and survival prognosis in early gastric cancer patients: A retrospective study

BACKGROUND Early gastric cancer(EGC)is a common malignant tumor of the digestive system,and its lymph node metastasis and survival prognosis have been concerning.By retrospectively analyzing the clinical data of EGC patients,we can better under-stand the status of lymph node metastasis and its impact on survival and prog-nosis.AIM To evaluate the prognosis of EGC patients and the factors that affect lymph node METHODS The clinicopathological data of 1011 patients with EGC admitted to our hospital between January 2015 and December 2023 were collected in a retrospective cohort study.There were 561 males and 450 females.The mean age was 58±11 years.The patient underwent radical gastrectomy.The status of lymph node metastasis in each group was determined according to the pathological examination results of surgical specimens.The outcomes were as follows:(1)Lymph node metastasis in EGC patients;(2)Analysis of influencing factors of lymph node metastasis in EGC;and(3)Analysis of prognostic factors in patients with EGC.Normally distributed measurement data are expressed as mean±SD,and a t test was used for comparisons between groups.The data are expressed as absolute numbers or percentages,and the chi-square test was used for comparisons between groups.Rank data were compared using a nonparametric rank sum test.A log-rank test and a logistic regression model were used for univariate analysis.A logistic stepwise regression model and a Cox stepwise regression model were used for multivariate analysis.The Kaplan-Meier method was used to calculate the survival rate and construct survival curves.A log-rank test was used for survival analysis.RESULTS Analysis of influencing factors of lymph node metastasis in EGC.The results of the multifactor analysis showed that tumor length and diameter,tumor site,tumor invasion depth,vascular thrombus,and tumor differentiation degree were independent influencing factors for lymph node metastasis in patients with EGC(odds ratios=1.80,1.49,2.65,5.76,and 0.60;95%CI:1.29–2.50,1.11–2.00,1.81–3.88,3.87-8.59,and 0.48-0.76,respectively;P<0.05).Analysis of prognostic factors in patients with EGC.All 1011 patients with EGC were followed up for 43(0–13)months.The 3-year overall survival rate was 97.32%.Multivariate analysis revealed that age>60 years and lymph node metastasis were independent risk factors for prognosis in patients with EGC(hazard ratio=9.50,2.20;95%CI:3.31-27.29,1.00-4.87;P<0.05).Further analysis revealed that the 3-year overall survival rates of gastric cancer patients aged>60 years and≤60 years were 99.37%and 94.66%,respectively,and the difference was statistically significant(P<0.05).The 3-year overall survival rates of patients with and without lymph node metastasis were 95.42%and 97.92%,respectively,and the difference was statistically significant(P<0.05).CONCLUSION The lymph node metastasis rate of EGC patients was 23.64%.Tumor length,tumor site,tumor infiltration depth,vascular cancer thrombin,and tumor differentiation degree were found to be independent factors affecting lymph node metastasis in EGC patients.Age>60 years and lymph node metastasis are independent risk factors for EGC prognosis.

Reclassification and Nomenclature of Common Pathogenic Fungi

The accurate identification of pathogenic fungi is crucial for diagnosing and treating fungal infections. Recent advancements in molecular biotechnology, phylogenetic analysis, and the requirements of the Melbourne Code have led to changes in the classification and naming of fungi. These changes have caused significant confusion for medical laboratories and clinical personnel. This article summarizes the classification and new names of common pathogenic fungi to enhance fungi identification skills and provide accurate information for clinical diagnosis and treatment.

Compare clinical efficacy and safety of neoadjuvant therapy and neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Meta-analysis

BACKGROUND To compare the efficacy and safety of total neoadjuvant therapy(TNT)and neoadjuvant chemoradiotherapy(nCRT)in the treatment of middle and low locally advanced rectal cancer.Our study will systematically collect and integrate studies to evaluate the ability of these two treatments to improve tumor shrinkage rates,surgical resection rates,tumor-free survival,and severe adverse events.AIM To provide clinicians and patients with more reliable treatment options to optimize treatment outcomes and quality of life for patients with locally advanced rectal cancer by comparing the advantages and disadvantages of the two treatment options.METHODS A full search of all clinical studies on the effectiveness and safety of TNT and nCRT for treating locally advanced rectal cancer identified in Chinese(CNKI,Wanfang,China Biomedical Literature Database)and English(PubMed,Embase)databases was performed.Two system assessors independently screened the studies according to the inclusion and exclusion criteria.Quality evaluation and RESULTS Finally,14 studies were included,six of which were randomized controlled studies.A total of 3797 patients were included,including 1865 in the TNT group and 1932 in the nCRT group.The two sets of baseline data were comparable.The results of the meta-analysis showed that the pCR rate[odds ratio(OR)=1.57,95%confidence interval(CI):1.30-1.90,P<0.00001],T stage degradation rate(OR=2.16,95%CI:1.63-2.57,P<0.00001),and R0 resection rate(OR=1.42,95%CI:1.09-1.85,P=0.009)were significantly greater in the nCRT group than in the nCRT group.There was no significant difference in the incidence of grade 3/4 acute toxicity or perioperative complications between the two groups.The 5-year OS[hazard ratio(HR)=0.84,95%CI:0.69-1.02,P=0.08]and DFS(HR=0.94,95%CI:0.03-1.39,P=0.74)of the TNT group were similar to those of the nCRT group.CONCLUSION TNT has greater clinical efficacy and safety than nCRT in the treatment of locally advanced rectal cancer.

Comparison efficacy and safety of total laparoscopic gastrectomy and laparoscopically assisted total gastrectomy in treatment of gastric cancer

BACKGROUND The development of laparoscopic technology has provided a new choice for surgery of gastric cancer(GC),but the advantages and disadvantages of laparoscopic total gastrectomy(LTG)and laparoscopic-assisted total gastrectomy(LATG)in treatment effect and safety are still controversial.The purpose of this study is to compare the efficacy and safety of the two methods in the treatment of GC,and to provide a basis for clinical decision-making.AIM To compare the efficacy of totally LTG(TLTG)and LATG in the context of radical gastrectomy for GC.Additionally,we investigated the safety and feasibility of the total laparoscopic esophagojejunostomy technique.METHODS Literature on comparative studies of the above two surgical methods for GC(TLTG group and LATG group)published before September 2022 were searched in the PubMed,Web of Science,Wanfang Database,CNKI,and other Chinese and English databases.In addition,the following search keywords were used:Gastric cancer,total gastrectomy,total laparoscopy,laparoscopy-assisted,esophagojejunal anastomosis,gastric/stomach cancer,total gastrectomy,totally/completely laparoscopic,laparoscopic assisted/laparoscopy assisted/laparoscopically assisted,and esophagojejunostomy/esophagojejunal anastomosis.Review Manager 5.3 software was used for the meta-analysis after two researchers independently screened the literature,extracted the data,and evaluated the risk of bias in the included studies.RESULTS After layer-by-layer screening,258 pieces of literature were recovered,and 11 of those pieces were eventually included.This resulted in a sample size of 2421 instances,with 1115 cases falling into the TLTG group and 1306 cases into the LATG group.Age or sex differences between the two groups were not statistically significant,according to the meta-analysis,however the average body mass index of the TLTG group was considerably higher than that of the LATG group(P=0.01).Compared with those in the LATG group,the incision length in the TLTG group was significantly shorter(P<0.001),the amount of intraoperative blood loss was significantly lower(P=0.003),the number of lymph nodes removed was significantly greater(P=0.04),and the time of first postoperative feeding and postoperative hospitalization were also significantly shorter(P=0.03 and 0.02,respectively).There were no significant differences in tumor size,length of proximal incisal margin,total operation time,anastomotic time,postoperative pain score,postoperative anal exhaust time,postoperative anastomosis-related complications(including anastomotic fistula,anastomotic stenosis,and anastomotic hemorrhage),or overall postoperative complication rate(P>0.05).CONCLUSION TLTG and esophagojejunostomy are safe and feasible.Compared with LATG,TLTG has the advantages of less trauma,less bleeding,easier access to lymph nodes,and faster postoperative recovery,and TLTG is also suitable for obese patients.

尾加压素Ⅱ对自发性高血压大鼠血管外膜成纤维细胞增殖活性及细胞外信号调节激酶1/2磷酸化的影响

目的研究尾加压素Ⅱ(UⅡ)对自发性高血压大鼠(SHR)血管外膜成纤维细胞增殖活性的影响,并进一步探讨其可能涉及的信号转导通路。方法用胸腺嘧啶掺入法(3H-TdR)观察UⅡ诱导的SHR大鼠血管外膜成纤维细胞的增殖活性,及UⅡ受体拮抗剂Urantide、细胞外信号调节激酶1/2(ERK1/2)特异性的抑制剂PD98059对UⅡ诱导SHR大鼠血管外膜成纤维细胞增殖活性的影响;用免疫印迹技术观察UⅡ诱导后ERK1/2的磷酸化,及Urantide、PD98059对ERK1/2磷酸化的影响。结果UⅡ可以剂量依赖性地诱导SHR大鼠血管外膜成纤维细胞的增殖活性,且这一作用可以完全及部分被Urantide、PD98059抑制;UⅡ可以时间依赖性地诱导血管外膜成纤维细胞ERK1/2的磷酸化,且这一作用可以完全被Urantide、PD98059抑制。结论UⅡ可以诱导SHR大鼠血管外膜成纤维细胞的增殖活性,且该过程部分由ERK1/2信号通路所介导。

Electroacupuncture preconditioning protects against focal cerebral ischemia/reperfusion injury via suppression of dynamin-related protein 1

Electroacupuncture preconditioning at acupoint Baihui （GV20） can reduce focal cerebral ischemia/reperfusion injury. However, the precise protective mechanism remains unknown. Mitochondrial fission mediated by dynamin-related protein 1 （Drp1） can trigger neuronal apoptosis following cerebral ischemia/reperfusion injury. Herein, we examined the hypothesis that electroacupuncture pretreatment can regulate Drp1, and thus inhibit mitochondrial fission to provide cerebral protection. Rat models of focal cerebral ischemia/reperfusion injury were established by middle cerebral artery occlusion at 24 hours after 5 consecutive days of preconditioning with electroacupuncture at GV20 （depth 2 mm, intensity 1 mA, frequency 2/15 Hz, for 30 minutes, once a day）. Neurological function was assessed using the Longa neurological deficit score. Pathological changes in the ischemic penumbra on the injury side were assessed by hematoxylin-eosin staining. Cellular apoptosis in the ischemic penumbra on the injury side was assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling staining. Mitochondrial ultrastructure in the ischemic penumbra on the injury side was assessed by transmission electron microscopy. Drp1 and cytochrome c expression in the ischemic penumbra on the injury side were assessed by western blot assay. Results showed that electroacupuncture preconditioning decreased expression of total and mitochondrial Drp1, decreased expression of total and cytosolic cytochrome c, maintained mitochondrial morphology and reduced the proportion of apoptotic cells in the ischemic penumbra on the injury side, with associated improvements in neurological function. These data suggest that electroacupuncture preconditioning-induced neuronal protection involves inhibition of the expression and translocation of Drp1.

Selective brain hypothermia-induced neuroprotection against focal cerebral ischemia/reperfusion injury is associated with Fis1 inhibition

Selective brain hypothermia is considered an effective treatment for neuronal injury after stroke,and avoids the complications of general hypothermia.However,the mechanisms by which selective brain hypothermia affects mitochondrial fission remain unknown.In this study,we investigated the effect of selective brain hypothermia on the expression of fission 1 (Fis1) protein,a key factor in the mitochondrial fission system,during focal cerebral ischemia/reperfusion injury.Sprague-Dawley rats were divided into four groups.In the sham group,the carotid arteries were exposed only.In the other three groups,middle cerebral artery occlusion was performed using the intraluminal filament technique.After 2 hours of occlusion,the filament was slowly removed to allow blood reperfusion in the ischemia/reperfusion group.Saline,at 4℃ and 37℃,were perfused through the carotid artery in the hypothermia and normothermia groups,respectively,followed by restoration of blood flow.Neurological function was assessed with the Zea Longa 5-point scoring method.Cerebral infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride staining,and apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining.Fis1 and cytosolic cytochrome c levels were assessed by western blot assay.Fis1 mRNA expression was assessed by quantitative reverse transcription-polymerase chain reaction.Mitochondrial ultrastructure was evaluated by transmission electron microscopy.Compared with the sham group,apoptosis,Fis1 protein and mRNA expression and cytosolic cytochrome c levels in the cortical ischemic penumbra and cerebral infarct volume were increased after reperfusion in the other three groups.These changes caused by cerebral ischemia/reperfusion were inhibited in the hypothermia group compared with the normothermia group.These findings show that selective brain hypothermia inhibits Fis1 expression and reduces apoptosis,thereby ameliorating focal cerebral ischemia/reperfusion injury in rats.Experiments were authorized by the Ethics Committee of Qingdao Municipal Hospital of China (approval No.2019008).

Adaptive and regulatory mechanisms in aged rats with postoperative cognitive dysfunction

Inflammation may play a role in postoperative cognitive dysfunction. 5＇ Adenosine monophos- phate-activated protein kinase, nuclear factor-kappa B, interleukin-1β, and tumor necrosis factor-a are involved in inflammation. Therefore, these inflammatory mediators may be involved in postoperative cognitive dysfunction. Western immunoblot analysis revealed 5＇ adenosine mo- nophosphate-activated protein kinase and nuclear factor-kappa B in the hippocampus of aged rats were increased 1-7 days after splenectomy. Moreover, interleukin-1β and tumor necrosis fac- tor-α were upregulated and gradually decreased. Therefore, these inflammatory mediators may participate in the splenectomy model of postoperative cognitive dysfunction in aged rats.

Chemotherapy and resection for gastric cancer with synchronous liver metastases

AIM: To investigate the effect of surgery and chemotherapy for gastric cancer with multiple synchronous liver metastases (GCLM). METHODS: A total of 114 patients were entered in this study, and 20 patients with multiple synchronous liver metastases were eligible. After screening with preoperative chemotherapy, 20 patients underwent curative gastrectomy and hepatectomy for GCLM; 14 underwent major hepatectomy, and the remaining six underwent minor hepatectomy. There were 94 patients without aggressive treatment, and they were in the non-operative group. Two regimens of perioperative chemotherapy were used: S-1 and cisplatin (SP) in 12 patients, and docetaxel, cisplatin and 5-fluorouracil (DCF) in eight patients. These GCLM patients were given preoperative chemotherapy consisting of two courses chemotherapy of SP or DCF regimens. After chemotherapy, gastrectomy and hepatectomy were preformed. Evaluation of patient survival was by follow-up contact using telephone and outpatient records. All patients were assessed every 3 mo during the first year and every 6 mo thereafter. RESULTS: Twenty patients underwent gastrectomy and hepatectomy and completed their perioperative chemotherapy and hepatic arterial infusion before and after surgery. Ninety-four patients had no aggressive treatment of liver metastases because of technical difficulties with resection and severe cardiopulmonary dysfunction. In the surgery group, there was no toxicity greater than grade 3 during the course of chemotherapy. The response rate was 100% according to the Response Evaluation Criteria in Solid Tumors Criteria. For all 114 patients, the overall survival rate was 8.0%, 4.0%, 4.0% and 4.0% at 1, 2, 3 and 4 years, respectively, with a median survival time (MST) of 8.5 mo (range: 0.5-48 mo). For the 20 patients in the surgery group, MST was 22.3 mo (range: 4-48 mo). In the 94 patients without aggressive treatment, MST was 5.5 mo (range: 0.5-21 mo). There was a significant difference between the surgery and unresectable patients (P = 0.000). Three patients in surgery group were still alive at the end of the cut-off date. CONCLUSION: Perioperative weekly DCF and SP achieved a good response, and combined with surgery, they could improve prognosis of GCLM.