BACKGROUND:Elderly people with mild cognitive impairment experience a decline in postural control ability due to cognitive function decline,making them more prone to falls.The dual-task paradigm,which more closely mirrors daily life,is often used to assess postural control ability.However,previous dual-task studies on cognition and postural control in elderly people with mild cognitive impairment have mainly focused on the external manifestations of postural control,with direct evidence of central nervous mechanisms still lacking.OBJECTIVE:To investigate the activation characteristics of the cerebral somatic sensorimotor cortex in the elderly people with mild cognitive impairment while performing the dual task of stance postural control and spatial working memory.METHODS:Participants were screened using the Montreal Cognitive Assessment,enrolling 16 elderly people with mild cognitive impairment and 17 healthy older people.They performed five task tests:spatial working memory,dual-feet balance stance,Romberg stance,dual task of dual-feet balance stance and spatial working memory,and dual task of Romberg stance and spatial working memory.Functional near-infrared spectroscopy and a three-dimentional force platform were used simultaneously to collect data on cerebral cortex(20 channels)hemodynamics and center of pressure swing trajectory.RESULTS AND CONCLUSION:In Romberg stance,dual task of dual-feet balance stance and spatial working memory,and dual task of Romberg stance and spatial working memory tasks,center of pressure displacements in anterior-posterior and medial-lateral directions were significantly greater in mild cognitive impairment elderly people than that in normal elder people(P<0.05).In dual task of dual-feet balance stance and spatial working memory task,ΔHbO2 at channel 15(right pre-motor cortex and supplementary motor area)was significantly greater in mild cognitive impairment elderly people than that in normal elder people(P<0.05).In dual task of Romberg stance and spatial working memory task,ΔHbO2 at channels 15 and 17(right pre-motor cortex and supplementary motor area)was significantly greater in the elderly people with mild cognitive impairment compared with the healthy older people(P<0.05).In dual task of Romberg stance and spatial working memory task,a significantly positive correlation in the elderly people with mild cognitive impairment(r=0.659,P<0.05)and a strong positive correlation in the healthy older people were observed between center of pressure displacement in medial-lateral direction and ΔHbO2 at channel 15(r=0.840,P<0.05).The results indicate that compared with the cognitively normal healthy older people,the elderly people with mild cognitive impairment showed weaker stance postural control capability during the dual task of stance postural control and spatial working memory,with higher activation levels in the right pre-motor cortex and supplementary motor area.The increased brain resource allocation for lateral postural control may represent the brain compensation mechanism in the elderly people with mild cognitive impairment due to cognitive decline leading to weakened stance postural control ability.

AIM:To explore the causal association between the counts of five types of white blood cells—neutrophils,monocytes,eosinophils,baso-phils,and lymphocytes—and venous thromboem-bolism(VTE).METHODS:Mendelian randomization(MR)analysis method was used,with genetic vari-ants associated with the five types of white blood cells as instrumental variables,and venous throm-boembolism occurrence risk as the outcome vari-able,inverse variance-weighted(IVW)method was employed as the primary analysis method,with MR-Egger regression,weighted median(WM),sim-ple model,and weighted mode methods used as supplements,to analyze the causal association be-tween the counts of five types of white blood cells and VTE,followed by reverse MR analysis.RE-SULTS:Neutrophil and lymphocyte counts are caus-ally associated with the risk of VTE.For neutrophil count,the IVW estimate(OR=0.867,95%CI:0.761-0.981,P=0.031),MR-Egger estimate(OR=0.754,95%CI:0.571-0.996,P=0.048),weighted median es-timate(OR=0.846,95%CI:0.729-0.981,P=0.027),and weighted model estimate(OR=0.748,95%CI:0.595-0.942,P=0.014)were calculated.For lympho-cyte count,the IVW estimate(OR=0.838,95%CI:0.741-0.949,P=0.005)and weighted median esti-mate(OR=0.024,95%CI:0.718-0.977,P=0.024)were calculated.Reverse MR analysis showed a causal association between the risk of VTE and neu-trophil count,the IVW estimate(OR=0.989,95%CI:0.980-0.999,P=0.024).CONCLUSION:Neutrophil and lymphocyte counts are related to the risk of VTE,and decrease in neutrophil and lymphocyte numbers may increase the risk of VTE.VTE occur-rence risk is associated with neutrophil count,and reducing the risk of VTE occurrence may increase neutrophil count.Further research is needed to un-derstand the underlying biological mechanisms be-hind this relationship.

AIM:To explore the causal association between the counts of five types of white blood cells—neutrophils,monocytes,eosinophils,baso-phils,and lymphocytes—and venous thromboem-bolism(VTE).METHODS:Mendelian randomization(MR)analysis method was used,with genetic vari-ants associated with the five types of white blood cells as instrumental variables,and venous throm-boembolism occurrence risk as the outcome vari-able,inverse variance-weighted(IVW)method was employed as the primary analysis method,with MR-Egger regression,weighted median(WM),sim-ple model,and weighted mode methods used as supplements,to analyze the causal association be-tween the counts of five types of white blood cells and VTE,followed by reverse MR analysis.RE-SULTS:Neutrophil and lymphocyte counts are caus-ally associated with the risk of VTE.For neutrophil count,the IVW estimate(OR=0.867,95%CI:0.761-0.981,P=0.031),MR-Egger estimate(OR=0.754,95%CI:0.571-0.996,P=0.048),weighted median es-timate(OR=0.846,95%CI:0.729-0.981,P=0.027),and weighted model estimate(OR=0.748,95%CI:0.595-0.942,P=0.014)were calculated.For lympho-cyte count,the IVW estimate(OR=0.838,95%CI:0.741-0.949,P=0.005)and weighted median esti-mate(OR=0.024,95%CI:0.718-0.977,P=0.024)were calculated.Reverse MR analysis showed a causal association between the risk of VTE and neu-trophil count,the IVW estimate(OR=0.989,95%CI:0.980-0.999,P=0.024).CONCLUSION:Neutrophil and lymphocyte counts are related to the risk of VTE,and decrease in neutrophil and lymphocyte numbers may increase the risk of VTE.VTE occur-rence risk is associated with neutrophil count,and reducing the risk of VTE occurrence may increase neutrophil count.Further research is needed to un-derstand the underlying biological mechanisms be-hind this relationship.

BACKGROUND:Elderly people with mild cognitive impairment experience a decline in postural control ability due to cognitive function decline,making them more prone to falls.The dual-task paradigm,which more closely mirrors daily life,is often used to assess postural control ability.However,previous dual-task studies on cognition and postural control in elderly people with mild cognitive impairment have mainly focused on the external manifestations of postural control,with direct evidence of central nervous mechanisms still lacking.OBJECTIVE:To investigate the activation characteristics of the cerebral somatic sensorimotor cortex in the elderly people with mild cognitive impairment while performing the dual task of stance postural control and spatial working memory.METHODS:Participants were screened using the Montreal Cognitive Assessment,enrolling 16 elderly people with mild cognitive impairment and 17 healthy older people.They performed five task tests:spatial working memory,dual-feet balance stance,Romberg stance,dual task of dual-feet balance stance and spatial working memory,and dual task of Romberg stance and spatial working memory.Functional near-infrared spectroscopy and a three-dimentional force platform were used simultaneously to collect data on cerebral cortex(20 channels)hemodynamics and center of pressure swing trajectory.RESULTS AND CONCLUSION:In Romberg stance,dual task of dual-feet balance stance and spatial working memory,and dual task of Romberg stance and spatial working memory tasks,center of pressure displacements in anterior-posterior and medial-lateral directions were significantly greater in mild cognitive impairment elderly people than that in normal elder people(P<0.05).In dual task of dual-feet balance stance and spatial working memory task,ΔHbO2 at channel 15(right pre-motor cortex and supplementary motor area)was significantly greater in mild cognitive impairment elderly people than that in normal elder people(P<0.05).In dual task of Romberg stance and spatial working memory task,ΔHbO2 at channels 15 and 17(right pre-motor cortex and supplementary motor area)was significantly greater in the elderly people with mild cognitive impairment compared with the healthy older people(P<0.05).In dual task of Romberg stance and spatial working memory task,a significantly positive correlation in the elderly people with mild cognitive impairment(r=0.659,P<0.05)and a strong positive correlation in the healthy older people were observed between center of pressure displacement in medial-lateral direction and ΔHbO2 at channel 15(r=0.840,P<0.05).The results indicate that compared with the cognitively normal healthy older people,the elderly people with mild cognitive impairment showed weaker stance postural control capability during the dual task of stance postural control and spatial working memory,with higher activation levels in the right pre-motor cortex and supplementary motor area.The increased brain resource allocation for lateral postural control may represent the brain compensation mechanism in the elderly people with mild cognitive impairment due to cognitive decline leading to weakened stance postural control ability.

Objective:To investigate the effect of ginkgolide B(GB)on astrocyte(AST)phagocytosis of myelin debris,and to investigate the mechanism of this functional therapy to demyelination by targeting AST.Methods:In vitro culture of AST,and divided AST into three groups:Control group,Myelin debris(Debris)group and Debris+GB group,incubed them in a constant temperature CO2 cell culture incubator for 24 hours,and then detected relevant indicators to observe the effect of GB on AST on phagocytic myelin debris.Results:Compared to the phagocytosis of myelin debris by primary AST,GB could effectively promote the phagocytosis by AST and show enhanced ABCA-1 expression(both P<0.05).Phagocytosis of myelin debris had no effect on the secretion of inflammatory cytokines by in vitro cultured AST.Debris+GB increased the expressions of neurotrophic CNTF and B-FGF compared to Debris(both P<0.05).Furthermore,Debris+GB decreased Bax and Caspase-3,while increased Bcl-2 expression(all P<0.05).Conclusion:GB can promote the phagocytosis of myelin debris by AST,which may be related to the upregulation of ABCA-1.Meanwhile,phagocytosis of myelin debris by AST increases the expression of the neurotrophic factors and the inhibits the apoptosis of AST themselves.

Objective To evaluate the efficacy and safety of polyethylene glycol electrolyte powder(PEG)combined with linaclotide(Lin)for bowel preparation in elderly constipated patients before colonoscopy.Methods In this prospective,randomized controlled trial,90 elderly patients with constipation undergoing colonoscopy were recruited at our hospital from June 2022 to December 2023.Participants were randomly assigned to three groups(n=30 each):PEG-3L alone,PEG-3L+Lin,and PEG-2L+Lin.Primary outcome was Boston Bowel Preparation Scale(BBPS)score and secondary outcomes included adverse event rates,colonoscopy completion rate,withdrawal time,and polyp detection rate.Statistical analysis was performed using independent t-tests and chi-square tests.Results The PEG-3L+Lin group achieved significantly higher BBPS scores than both PEG-3L alone and PEG-2L+Lin groups did(both P<0.001).The PEG-2L+Lin group also outperformed the PEG-3L alone group in cleansing efficacy(90.0%vs.76.7%,P=0.008).The PEG-2L+Lin group demonstrated the best tolerability and lowest adverse event rate,the PEG-3L group had the longest withdrawal time(P<0.05),but the three groups showed no significant difference in polyp detection rates.Conclusion PEG combined with linaclotide significantly improves bowel cleansing in elderly constipated patients.PEG-2L+Lin regimen provides optimal balance between efficacy,safety,and tolerability,making it a preferable choice for this population.

ObjectiveTo investigate the incidence rate of primary liver cancer （PLC） and the progression of liver fibrosis in chronic hepatitis B （CHB） patients with low-level viremia （LLV） （HBV DNA<2 000 IU/mL but ≥20 IU/mL） after treatment adjustment， and to provide more robust evidence for clinical practice. MethodsA retrospective analysis was performed for the clinical data of LLV patients who initially received nucleos（t）ide analogue （NAs） for at least 48 weeks at the Fifth Medical Center of PLA General Hospital from August 2007 to April 2017 and subsequently underwent NAs adjustment due to LLV， and according to the virologic response after 48 weeks of treatment adjustment， the patients were divided into LLV group and complete virological response （CVR） group （HBV DNA<20 IU/mL）. The patients were followed up once every 3‍ ‍—‍ ‍6 months till the primary endpoint event of PLC or October 2024. The incidence rate of PLC and the progression of liver fibrosis were observed， and the progression of liver fibrosis was defined as an increase of ≥1 grade in fibrosis-4 （FIB-4） index. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups； the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to calculate the cumulative incidence rate of PLC， and the Log-rank test was used for comparison between groups； the Cox regression analysis was used to investigate the risk factors for PLC， and the Logistic regression analysis was used to investigate the influencing factors for the progression of liver fibrosis. ResultsA total of 307 patients were enrolled， with a mean age of 50.0 years， and the male patients accounted for 80.5%. After 48 weeks of treatment with the adjusted NAs regimen， 254 patients （82.7%） achieved CVR， and 53 patients （17.3%） still had LLV. For the LLV group， the incidence rate of PLC was 30.2% and the rate of liver fibrosis progression was 22.6%， while for the CVR group， the incidence rate of PLC was only 13.4%， and the rate of liver fibrosis progression was 7.5%. The multivariate regression analyses showed that LLV was an independent risk factor for the onset of PLC （hazard ratio=2.623， 95% confidence interval ［CI］： 1.315‍ ‍—‍ ‍5.234， P=0.006） and the progression of liver fibrosis （odds ratio=3.213， 95%CI： 1.385‍ ‍—‍ ‍7.455， P=0.007）. ConclusionActive adjustment of treatment is needed immediately after the diagnosis of LLV to improve CVR， and if LLV persists after treatment adjustment， it is necessary to enhance the monitoring of liver fibrosis progression and PLC， so as to facilitate early diagnosis and treatment.

BACKGROUND:Hydroxy safflower yellow A has anti-ischemia,anti-oxidation,anti-thrombotic and anti-inflammatory effects.Whether it affects neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation is still unclear. OBJECTIVE:To investigate the protective effect of hydroxy safflower yellow A on neuronal pyroptosis and its mechanism. METHODS:HT22 cells in logarithmic growth phase were randomly divided into five groups:normal group,model group,hydroxy safflower yellow A group,colivelin group,and colivelin+hydroxy safflower yellow A group.HT22 cells were treated with glucose-oxygen deprivation/reglucose-reoxygenation to establish neuronal pyroptosis model,and then treated with STAT3 agonist Colivelin and hydroxy safflower yellow A.JC-1 probe was employed to assess changes in mitochondrial membrane potential.Reactive oxygen species kit was used to determine the content of reactive oxygen species in cells.GSDMD/TUNEL staining was conducted to observe cell pyroptosis.Immunofluorescence analysis was performed to detect STAT3 and GSDMD protein expression.RT-PCR was utilized for assessing mRNA expression levels of STAT3,NLRP3,and Caspase-1.Western blot assay was utilized to measure the protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β. RESULTS AND CONCLUSION:(1)Compared with the normal group,the number of pyroptotic cells increased in HT22 cells in the model group along with a significant increase in protein expression levels of p-STAT3,NLRP3,Cleaved-caspase-1,GSDMD,and interleukin-1β.Compared with the model group,the number of pyroptotic cells reduced,and the expression of pyroptosis-related proteins significantly decreased in the hydroxy safflower yellow A group.(2)In comparison with the model group,pyroptosis worsened in the colivelin group where mitochondrial membrane potential decreased along with elevated reactive oxygen species content and increased mRNA expression levels of STAT3,NLRP3,and Caspase-1,as well as increased protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β.Compared with the Colivelin group,above indexes were improved in the colivelin+hydroxy safflower yellow A group.These results suggest that hydroxy safflower yellow A plays a neuroprotective role through STAT3 signaling pathway to inhibit HT22 pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment.

Objective To evaluate the efficacy and safety of polyethylene glycol electrolyte powder(PEG)combined with linaclotide(Lin)for bowel preparation in elderly constipated patients before colonoscopy.Methods In this prospective,randomized controlled trial,90 elderly patients with constipation undergoing colonoscopy were recruited at our hospital from June 2022 to December 2023.Participants were randomly assigned to three groups(n=30 each):PEG-3L alone,PEG-3L+Lin,and PEG-2L+Lin.Primary outcome was Boston Bowel Preparation Scale(BBPS)score and secondary outcomes included adverse event rates,colonoscopy completion rate,withdrawal time,and polyp detection rate.Statistical analysis was performed using independent t-tests and chi-square tests.Results The PEG-3L+Lin group achieved significantly higher BBPS scores than both PEG-3L alone and PEG-2L+Lin groups did(both P<0.001).The PEG-2L+Lin group also outperformed the PEG-3L alone group in cleansing efficacy(90.0%vs.76.7%,P=0.008).The PEG-2L+Lin group demonstrated the best tolerability and lowest adverse event rate,the PEG-3L group had the longest withdrawal time(P<0.05),but the three groups showed no significant difference in polyp detection rates.Conclusion PEG combined with linaclotide significantly improves bowel cleansing in elderly constipated patients.PEG-2L+Lin regimen provides optimal balance between efficacy,safety,and tolerability,making it a preferable choice for this population.

Objective To explore the role of mitophagy in pancreatic cancer cachexia-induced muscle atrophy and its underlying mechanism.Methods Six male C57BL/6J mice(8 weeks old,weighing 20～30 g)were equally and randomly divided into a control group(intrapancreatic injection of normal saline)and a cachexia group(orthotopic pancreatic injection of KPC1199 cells).After successful model establishment,gastrocnemius muscles were harvested for transmission electron microscopy(TEM)to assess mitochondrial ultrastructure.Western blotting was performed to quantify mitochondrial respiratory chain complexes(Ⅰ～Ⅳ)and autophagy-related proteins,while immunofluorescence staining was conducted to evaluate mitochondrial-lysosomal colocalization.In in vitro experiments,C2C12 myoblasts were differentiated into myotubes,and then divided into a control group(standard culture)and a cachexia group(co-cultured with KPC1199 cells for 48 h using transwell chambers).Mitochondrial-lysosomal colocalization and autophagy-related protein expression were analyzed with immunofluorescence assay and Western blotting.The mitochondrial division inhibitor Mdivi-1(20 μmol/L)was added to the co-culture system to assess its myotube diameter.Results Compared to the control mice,the cachectic mice exhibited mitochondrial swelling,reduced cristae density,and significantly increased mitochondrial-lysosomal colocalization in gastrocnemius muscle(P<0.05).Western blotting revealed the expression levels of mitochondrial respiratory chain proteins complexⅠ(1.00±0.04 vs 0.51±0.04,P<0.05),complexⅡ(1.00±0.13 vs 0.73±0.15,P<0.05),complexⅢ(1.00±0.20 vs 0.64±0.01,P<0.05),complexⅣ(1.00±0.06 vs 0.65±0.02,P<0.05)and PGC1α(1.00±0.03 vs 0.62±0.06,P<0.05)were decreased,and the levels of mitophagy markers,LC3-Ⅰ/Ⅱ(1.00±0.14 vs 1.65±0.25,P<0.05),PINK1(1.00±0.11 vs 1.51±0.05,P<0.05),and BNIP3(1.00±0.22 vs 2.02±0.10,P<0.05)were elevated when compared to the control.In the C2C12 myotube model,tumor cell co-culture increased mitochondrial-lysosomal colocalization and upregulated mitophagy-related protein expression(P<0.05),consistent with the in vivo findings.Mdivi-1 treatment increased myotube diameter from 220.6±35.5 μm to 315.0±39.1 μm(R2=0.666 5,P<0.05).Conclusion Mitophagy is activated in pancreatic cancer cachexia-induced muscle atrophy.Inhibiting mitophagy can effectively alleviate muscle atrophy induced by pancreatic cancer cachexia.