ObjectiveTo investigate the protective effect of α-ketoglutarate （α-KG） on hepatic lipid deposition in offspring caused by arsenic exposure during pregnancy. Methods8-week-old institute of cancer research （ICR） mice were mated in a ratio of 2∶1 between females and males， and the detection of vaginal plugs confirmed pregnant. A total of 32 pregnant mice were randomly divided into four groups： control group， arsenic group， α-KG group， arsenic+α-KG group. On gestational day 0-16 （GD0-GD16）， the arsenic and arsenic+α-KG groups were exposed to sodium arsenite （NaAsO₂ ，15 mg/L） in drinking water everyday， and the α-KG and arsenic+α-KG groups were gavaged with α-KG （2 g/kg） everyday. On GD16， pregnant mice were euthanized to collect fetal liver， and fetal body weight and crown-rump length were measured. Gene expression differences between the control group and the arsenic group were analyzed by transcriptome. The total triglycerides （TGs） and subtypes in fetal liver were detected by liquid chromatography tandem mass spectrometry （LC-MS/MS）. Oil red O staining was used to observe the histopathological changes in the liver. Quantitative polymerase chain reaction （qPCR） was used to detect the expression level of genes related to lipid synthesis， transport， and degradation， and phosphatidylinositol 3' -kinase/ protein kinase B （PI3K/AKT） in the liver of fetus. ResultsTranscriptomics analysis showed that 2 144 genes were downregulated and 1 675 genes were upregulated in the arsenic exposed fetal liver； body weight and crown-rump length were reduced （P_TuKey<0.05）； the level of hepatic TGs was elevated in arsenic group （P_TuKey<0.05）； oil-red O staining showed a significant increase in lipid droplets in arsenic group （P_TuKey<0.01）； the expression of lipid synthesis-related genes were significantly upregulated （P_TuKey<0.05）； the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated （P_TuKey<0.05）； the expression of PI3K， AKT decreased（P_TuKey<0.05）. Compared with the arsenic group， the body weight and crown-rump length of fetus increased in the arsenic+α-KG group （P_TuKey<0.05）； the level of hepatic TGs decreased in the arsenic+α-KG group （P_TuKey<0.05）； oil red O staining showed lipid droplets significantly decreased （P_TuKey<0.01）； the expression of lipid synthesis-related genes were downregulated （P_TuKey<0.05）， the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated （P_TuKey<0.05）； the expression levels of PI3K and AKT increased （P_TuKey<0.05）. Conclusionα-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through activating PI3K/AKT signaling pathway.

Objective To analyze the current status of outcome measures in randomized controlled trials(RCTs)of acupuncture treatment for vascular dementia(VD)and promote the development of a standardized set of outcome measures.Methods Chinese and English literature databases were searched,including the Chinese Medical Periodical Full-Text Database,the Chinese Biology Medicine disc,China National Knowledge Infrastructure,Wanfang Data,VIP Database,PubMed,Embase,the Cochrane Library,MEDLINE,Web of Science,Chinese Clinical Trials Registry,and the International Traditional Medicine Clinical Trial Registry.Two researchers independently screened RCT literature on acupuncture treatment for VD between January 1,2015 and January 1,2025,risk of bias was assessed using the Cochrane Risk of Bias 2 tool.Extract basic study information,intervention measures,diagnostic criteria for both Chinese and Western medicine,TCM syndromes,and outcome measures.Summarize the indicator domains of RCT studies on acupuncture treatment for VD,and analyze the basic information and outcome measures of the included studies.Results A preliminary search identified 2,898 articles,of which 93 RCTs were ultimately included.These studies involved 84 outcome measures,covering six indicator domains:symptoms/signs(23.81%),traditional Chinese medicine(TCM)syndromes(3.57%),medical checkups(60.71%),quality of life(5.95%),safety assessment(4.76%),and prognosis follow-up(1.19%).A total of 91(97.85%)RCTs reported treatment duration,ranging from 2 to 24 weeks;72(77.42%)RCTs used clinical efficacy as the outcome indicator;11 studies(11.83%)reported safety assessments and adverse events.Conclusion Currently,the RCT study design for acupuncture treatment of VD lacks unified standards and has numerous methodological issues.These include insufficient description of sample size estimation processes,strong reliance on subjective rating scales,ambiguous definitions of primary and secondary outcome measures,incomplete integration of Chinese and Western medical indicators,and insufficient reflection of individualized syndrome differentiation and treatment characteristics.In addition,safety assessments and follow-up mechanisms remain relatively weak.Future research should focus on the essential nature of VD,establish a core set of indicators aligned with the clinical characteristics of traditional Chinese medicine,promote the scientific and standardized development of acupuncture research for VD,and provide more compelling evidence-based support for clinical practice.

Objective To investigate the mechanism by which 4-week high-intensity interval training(HIIT)regulates the mitochondrial unfolded protein response(UPRmt)in skeletal muscle and improves mitochondrial function in a rat model of chronic unpredictable mild stress(CUMS).Methods Male SPF-grade SD rats(6～8 weeks old)were divided randomly into control(C),model(M),HIIT+control(HC),and HIIT+model(HM)groups.Rats in the M and HM groups were subjected to CUMS for 8 weeks to establish a depression model,while rats in the HC and HM groups received HIIT for 5 d a week for 4 weeks.The exercise regimen consisted of 3 min high-speed(85％～90％Smax)combined with 1 min low-speed(50％～55％Smax)uninterrupted repetitive training(Smax is maximum training speed).Behavioral changes were evaluated at weeks 4 and 8.Tissue samples were taken 24 h after the last behavioral test and skeletal muscle mitochondria were examined by transmission electron microscopy.The ATP and reactive oxygen species(ROS)contents were measured by enzyme-linked immunosorbent assays and protein expression levels of activating transcription factor(ATF)4,ATF5,C/EBP homologous protein(CHOP),and heat shock protein 60(HSP60)were detected by Western blot.Results(1)The body mass,number of crossing grids,number of upright positions,sugar-water preference rate,and ATP content were significantly decreased in group M compared with group C(P＜0.01),while the number of damaged mitochondria,ROS content,ATF4,ATF5,CHOP,and HSP60 protein expression were significantly increased(P＜0.01).(2)After 4-weeks of HIIT intervention,the ATP content and ATF4 and ATF5 protein expression levels were significantly increased in the HC group compared with C group(P＜0.05,P＜0.01).The number of crossing grids,number of upright positions,sugar-water preference rate,ATP content,and ATF4 protein expression were significantly increased in the HM group compared with M group(P＜0.01),while the number of damaged mitochondria,ROS content,and ATF5,CHOP,and HSP60 protein expression levels were significantly decreased(P＜0.01).(3)After 4 weeks of HIIT intervention,the number of crossing grids in CUMS rats was significantly positively correlated with ATF4 protein expression,and ROS content was correlated with CHOP protein expression,number of damaged mitochondria,and ATF5 protein expression(|r|＞0.75,P＜0.01;|r|＞0.75,P＜0.05).Upright frequency was significantly negatively correlated with ATF5 and HSP60 protein expression,the number of crossing grids,the sugar-water preference rate,and the expression of CHOP and HSP60 proteins(|r|＜0.75,P＜0.05).Conclusions 4-week HIIT intervention can improve mitochondrial dysfunction and alleviate depressive-like behavior in CUMS rats by regulating skeletal muscle UPRmt.

Objective To investigate the mechanism by which 4-week high-intensity interval training(HIIT)regulates the mitochondrial unfolded protein response(UPRmt)in skeletal muscle and improves mitochondrial function in a rat model of chronic unpredictable mild stress(CUMS).Methods Male SPF-grade SD rats(6～8 weeks old)were divided randomly into control(C),model(M),HIIT+control(HC),and HIIT+model(HM)groups.Rats in the M and HM groups were subjected to CUMS for 8 weeks to establish a depression model,while rats in the HC and HM groups received HIIT for 5 d a week for 4 weeks.The exercise regimen consisted of 3 min high-speed(85％～90％Smax)combined with 1 min low-speed(50％～55％Smax)uninterrupted repetitive training(Smax is maximum training speed).Behavioral changes were evaluated at weeks 4 and 8.Tissue samples were taken 24 h after the last behavioral test and skeletal muscle mitochondria were examined by transmission electron microscopy.The ATP and reactive oxygen species(ROS)contents were measured by enzyme-linked immunosorbent assays and protein expression levels of activating transcription factor(ATF)4,ATF5,C/EBP homologous protein(CHOP),and heat shock protein 60(HSP60)were detected by Western blot.Results(1)The body mass,number of crossing grids,number of upright positions,sugar-water preference rate,and ATP content were significantly decreased in group M compared with group C(P＜0.01),while the number of damaged mitochondria,ROS content,ATF4,ATF5,CHOP,and HSP60 protein expression were significantly increased(P＜0.01).(2)After 4-weeks of HIIT intervention,the ATP content and ATF4 and ATF5 protein expression levels were significantly increased in the HC group compared with C group(P＜0.05,P＜0.01).The number of crossing grids,number of upright positions,sugar-water preference rate,ATP content,and ATF4 protein expression were significantly increased in the HM group compared with M group(P＜0.01),while the number of damaged mitochondria,ROS content,and ATF5,CHOP,and HSP60 protein expression levels were significantly decreased(P＜0.01).(3)After 4 weeks of HIIT intervention,the number of crossing grids in CUMS rats was significantly positively correlated with ATF4 protein expression,and ROS content was correlated with CHOP protein expression,number of damaged mitochondria,and ATF5 protein expression(|r|＞0.75,P＜0.01;|r|＞0.75,P＜0.05).Upright frequency was significantly negatively correlated with ATF5 and HSP60 protein expression,the number of crossing grids,the sugar-water preference rate,and the expression of CHOP and HSP60 proteins(|r|＜0.75,P＜0.05).Conclusions 4-week HIIT intervention can improve mitochondrial dysfunction and alleviate depressive-like behavior in CUMS rats by regulating skeletal muscle UPRmt.

Objective To explore the association between the ratio of red blood cell distribution width to albumin level(RAR)and the risk of non-valvular atrial fibrillation(NVAF)in patients with hyperuricemia.Methods A total of 8 277 patients with hyperuricemia who underwent physi-cal examinations at the Physical Examination Center of Northern Jiangsu People's Hospital from January 2021 to June 2024 were enrolled.From them,185 patients with AF were assigned into a case group,and 740 patients without AF were into a control group in a ratio of 1∶4 with propen-sity score matching(PSM).Logistic regression analysis,restricted cubic spline analysis,and sub-group analysis were employed to investigate the association between RAR and the risk of NVAF in hyperuricemic patients.Results The case group had significantly larger ratio of smoking,high-er levels of red blood cell distribution width,total bilirubin,hematocrit,and RAR index,but lower albumin,low-density lipoprotein cholesterol(LDL-C)and triglyceride(TG)levels,and smaller ra-tio of fatty liver than the control group(P＜0.01).Multivariate logistic regression analysis showed that the patients at Q2,Q3,and Q4 quartiles of RAR index have higher risk for AF than those at Q1 quartile(OR=2.843,OR=4.263,OR=7.801,P＜0.01).The effect of RAR index was significant when below the breakpoint of 2.85(OR=1.492,95％CI:1.151-1.993,P=0.004).Subgroup analysis indicated significant interactions between RAR index and age as well as smok-ing(P interaction＜0.05).The area under curve value of RAR index in predicting NVAF occurrence in male hyperuricemic patients was 0.679(95％CI:0.632-0.725).Conclusion In patients with hyperuricemia,a higher RAR index is associated with an increased risk of NVAF.RAR index has guiding significance for diagnosing male hyperuricemic patients complicated with AF.

OBJECTIVE To observe the effect of biapenem combined with moxifloxacin on treatment of the elderly patients with severe pneumonia based on the expression levels of microribonucleic acid(miR)-146a,miR-124 and miR-127.METHODS A total of 112 elderly patients with severe pneumonia who were treated in Jiangnan Uni-versity Affiliated Central Hospital from Jan.2021 to Oct.2023 were recruited as the research subjects and were randomly divided into the study group and the control group,with 56 cases in each group.The control group was treated with moxifloxacin,and the study group was treated with biapenem combined with moxifloxacin,and both groups were treated for 10 consecutive days.The curative effect was compared between the two groups after the treatment for 10 days,the rehabilitation status was observed;the curative effect,expression levels of miR-146a,miR-124 and miR-127 as well as inflammatory response were compared between the two groups before and after the treatment.The adverse reactions during the treatment were analyzed.RESULTS The total effective rate of the study group was 92.86％(52/56)after the treatment for 10 days,higher than 75.00％(42/56)of the control group(x2=10.693,P=0.001).The duration of cough,lung rales,recovery of body temperature and mechanical ventilation were shorter in the study group than those in the control group(P＜0.05).The expression levels of miR-146a and miR-127 of the two groups were lower after the treatment for 10 days than those before the treat-ment,the levels of whole blood white blood cell(WBC)counts,serum interleukin-6(IL-6)and procalcitonin(PCT)were lower after the treatment for 10 days than those before the treatment;the levels of the above indexes of the study group were lower than those of the control group(P＜0.05).The expression level of serum miR-124 of the two groups was higher after the treatment for 10 days than those before the treatment,and the level of the study group was higher than that of the control group(P＜0.05).The total incidence of adverse reactions was 14.29％in the study group,10.71％in the control group,and there was no significant difference(x2=1.298,P=0.255).CONCLUSION Biapenem combined with moxifloxacin can achieve exact effect on treatment of the elderly patients with severe pneumonia,regulate the expression levels of miR-146a,miR-124 and miR-127,inhibit the in-flammatory response of the body,and promote the rehabilitation,with the safety favorable.

Objective Neurological disorders,constitute the majority of acupuncture-treated ailments.By critically examining a comprehensive selection of high-quality clinical randomized controlled trials(RCTs)from both domestic and international sources,we aimed to uncover the prevailing hot research topic and potential future directions in acupuncture therapy for these conditions.Methods Four databases,including PubMed,Web of science,Cochrane Library and EMBASE were searched.The search period is set from the establishment of each database to November 30,2023.And the search content was RCTs of acupuncture for neurological diseases classified as Ⅰ and Ⅱ by the Chinese Academy of Sciences were extracted.Key aspects extracted included annual publication volume,journals,disease types,outcomes,conclusions,acupuncture methods and control groups.Results A total of 81 high-quality RCTs were identified,revealing a consistent annual publication trend of acupuncture for neurological disorders.Key journals contributing to this research were Cephalalgia,Clinical Rehabilitation and Clinical Journal Of Pain,etc.The studies predominantly focused on migraine and sequela of apoplexy with migraine days/frequency and Ashworth scale and its modifications as commonly used primary outcome indicators,respectively.Overall,there were 73 RCTs that concluded that acupuncture for neurologic disorders were effective,8 were ineffective.The acupuncture methods were diverse,encompassing acupuncture,individualized acupuncture and transcutaneous electrical nerve stimulation,etc.The control measures were also varied,featuring sham acupuncture,sham-acupoint and micro-needle,etc.Conclusion With the development of acupuncture RCTs,their international influence has expanded.Research has shifted from validation of effectiveness to exploration of mechanisms,and despite the expansion of the disease spectrum of acupuncture,acupuncture trials have yet to be regulated and standardized,and the assessment of acupuncture efficacy remains controversial and challenging for the discipline.It is recommended to promote multi-center cooperation and strengthen the training of trialists etc.to provide more high-quality clinical evidence.

Objective To analyze the current status of outcome measures in randomized controlled trials(RCTs)of acupuncture treatment for vascular dementia(VD)and promote the development of a standardized set of outcome measures.Methods Chinese and English literature databases were searched,including the Chinese Medical Periodical Full-Text Database,the Chinese Biology Medicine disc,China National Knowledge Infrastructure,Wanfang Data,VIP Database,PubMed,Embase,the Cochrane Library,MEDLINE,Web of Science,Chinese Clinical Trials Registry,and the International Traditional Medicine Clinical Trial Registry.Two researchers independently screened RCT literature on acupuncture treatment for VD between January 1,2015 and January 1,2025,risk of bias was assessed using the Cochrane Risk of Bias 2 tool.Extract basic study information,intervention measures,diagnostic criteria for both Chinese and Western medicine,TCM syndromes,and outcome measures.Summarize the indicator domains of RCT studies on acupuncture treatment for VD,and analyze the basic information and outcome measures of the included studies.Results A preliminary search identified 2,898 articles,of which 93 RCTs were ultimately included.These studies involved 84 outcome measures,covering six indicator domains:symptoms/signs(23.81%),traditional Chinese medicine(TCM)syndromes(3.57%),medical checkups(60.71%),quality of life(5.95%),safety assessment(4.76%),and prognosis follow-up(1.19%).A total of 91(97.85%)RCTs reported treatment duration,ranging from 2 to 24 weeks;72(77.42%)RCTs used clinical efficacy as the outcome indicator;11 studies(11.83%)reported safety assessments and adverse events.Conclusion Currently,the RCT study design for acupuncture treatment of VD lacks unified standards and has numerous methodological issues.These include insufficient description of sample size estimation processes,strong reliance on subjective rating scales,ambiguous definitions of primary and secondary outcome measures,incomplete integration of Chinese and Western medical indicators,and insufficient reflection of individualized syndrome differentiation and treatment characteristics.In addition,safety assessments and follow-up mechanisms remain relatively weak.Future research should focus on the essential nature of VD,establish a core set of indicators aligned with the clinical characteristics of traditional Chinese medicine,promote the scientific and standardized development of acupuncture research for VD,and provide more compelling evidence-based support for clinical practice.

OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin(IMP)on doxorubicin(DOX)resistance in breast cancer.METHODS The effects of maximum non-toxic concentration(100 μg/mL)of IMP combined with different concentrations of DOX(12.5,25,50,75,100 μg/mL)on the proliferation of MCF-7/DOX cells were determined by MTT method.MCF-7/DOX cells were divided into blank control group(1‰ dimethyl sulfoxide),DOX group(50 μg/mL),IMP+DOX group(100 μg/mL IMP+50 μg/mL DOX)and IMP group(100 μg/mL).mRNA and protein expressions of multidrug resistance protein 1(MDR1)and multidrug resistance-associated protein l in each group were measured.The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology,along with gene ontology(GO)enrichment analyses and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.RESULTS Compared with DOX alone,the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL,the reverse fold was 1.90,and the mRNA expression of MDR1 was significantly down-regulated(P＜0.05).The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification,multiple biological processes,and cell killing.The main pathway involved was the p53 signaling pathway,and the key targets mainly included constitutively photomorphogenic protein 1(COP1),cyclin E1(CCNE1),growth arrest and DNA damage-inducible protein 45A(GADD45A)and GADD45B.The results of the verification experiments showed that compared with DOX group,there was a trend of up-regulation of COP1 mRNA,and significant down-regulation of CCNE1,GADD45A,and GADD45B mRNA expression in IMP+DOX group(P＜0.05).CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1,CCNE1,GADD45A and GADD45B targets in the p53 signaling pathway.

Background When discussing the new concept of"pancreas spleen integration"in the early stage,we proposed that dampness heat stagnation in the spleen and deficiency due to stagnation are the traditional Chinese medicine(TCM)pathogenesis elements of pancreatitis-induced pancreatic ductal adenocarcinoma,among which dampness heat is the soil of pancreatitis deteriorates into pancreatic cancer.Objective Based on the TCM pathogenesis elements of pancreatitis to cancer with"damp heat"as the main factor,data mining technology was used to analyze the properties,channel conversion and active ingredients of heat-clearing Chinese medicines with anti-inflammatory and anti-tumor effects,and to summarize the drug characteristics of these Chinese medicines.To prospectively predict the use of drugs in the transformation process of pancreatitis to pancreatic cancer.Methods Taking Traditional Chinese Medicine(10th Edition of China Traditional Chinese Medicine Press)as the drug data source,66 heat-clearing herbs were searched in the literature database of CNKI and PubMed of inflammation * TCM or(inflammation+tumor)* TCM.The active ingredients were analyzed in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).Results Among the 66 heat-clearing drugs(excluding adjunct drugs),58 herbs had anti-inflammatory effects,53 herbs had anti-tumor effects,and 48 herbs had both anti-inflammatory and anti-tumor effects.The three groups of drugs were mainly bitter,sweet and pungent in five flavors,and were mainly liver,stomach,lung,heart and large intestine in meridian affinity.Five flavors and meridian affinity were highly similar.In the TCMSP,the"five principles of drug class"were used to screen the active ingredients of anti-inflammatory and anti-tumor drugs.A total of 1041 active ingredient data were screened,and 798 active ingredient data were screened after duplicate items were deleted.Top three active ingredients were Luteolin,Kaempferol and Acacetin.Conclusion Based on the analysis of five flavors,meridian affinity and active ingredients of heat-clearing medicine,this study found that the anti-inflammatory and anti-tumor effects of these Chinese herbs are highly overlapping,it has important guiding significance for the drug research and clinical prescription of pancreatitis-induced pancreatic ductal adenocarcinoma.