ObjectiveTo investigate the relationship between mitochondrial DNA copy number (mtDNAcn) and cognitive dysfunction, and its mediating role between type 2 diabetes mellitus (T2DM) and cognitive dysfunction. MethodsA case-control study was conducted from May 2019 to April 2021 at the Shanghai Yangpu District Central Hospital, China. A total of 193 subjects were recruited and divided into two groups based on the Montreal Cognitive Assessment (MoCA): normal control (NC) group (n=95) and cognitive impairment group (n=98). The prevalence of T2DM was determined on the basis of medical history, while mtDNAcn in peripheral blood samples was quantified using realtime fluorescent quantitative polymerase chain reaction. ResultsUnivariate analyses revealed that the mean mtDNAcn in the cognitive impairment group was 0.76±0.37, significantly lower than that in the NC group (1.06±0.45) (P<0.05). Logistic regression analyses showed that higher mtDNAcn was associated with a reduced risk of cognitive impairment (OR=0.315, 95%CI: 0.125‒0.795). Additionaly, a statistically significant positive correlation was observed between mtDNAcn and the total MoCA score (r=0.381, P<0.01). Morever, T2DM history (OR=2.741, 95%CI: 1.002‒7.497) and elevated glycosylated hemoglobin (HbA1c) levels (OR=1.796, 95%CI: 1.190‒2.711) were identified as risk factors for cognitive impairment. Mediation analyses indicated that mtDNAcn served as a mediator between T2DM/HbA1c and the risk of cognitive impairment, with proportions of mediating effect of 9.04% and 9.18%, respectively. ConclusionPatients with mild and moderate cognitive impairment have significantly lower mtDNAcn than those with normal cognitive function. Reduced mtDNAcn is an influencing factor for cognitive dysfunction and may play a mediating role in the association between T2DM and mild to moderate cognitive impairment.

BACKGROUND:Buqi Huoxue Compounds have significant clinical efficacy in treating ischemic stroke with Qi deficiency and phlegm stasis;however,the exact mechanism of action is not clear. OBJECTIVE:To observe the effect of Buqi Huoxue Compounds on the expression of vascular endothelial growth factor,basic fibroblast growth factor,brain-derived neurotrophic factor and autophagy related protein Beclin1 and p62 in a rat model of cerebral ischemia/reperfusion. METHODS:Forty male Sprague-Dawley rats were randomly divided into sham operation group,model group,Buqi Huoxue Compounds group and autophagy inhibitor group,with 10 rats in each group.In the latter three groups,a rat model of cerebral ischemia/reperfusion injury was established.The Buqi Huoxue Compounds group was intragastrically given Buqi Huoxue Compounds(6.49 g/kg,administered three times a day)2 hours after reperfusion;the autophagy inhibitor group was intragastrically given Buqi Huoxue Compounds(6.49 g/kg,administered three times a day)2 hours after reperfusion and intraperitoneally given 3-methyladenine 2 hours before gavage and at days 1-3 of gavage.The sham operation group and model group were given equal amounts of saline by gavage for 7 consecutive days.Neurological function,cerebral infarct volume,brain tissue morphology and expression of vascular endothelial growth factor,basic fibroblast growth factor,brain-derived neurotrophic factor and autophagy-related proteins Beclin1 and p62 in the ischemic cortical region of rats were detected at 24 hours after the final administration. RESULTS AND CONCLUSION:Zea-Longa scoring results showed that the neurological function of rats was severely damaged after modeling and neurological deficit of rats in the Buqi Huoxue Compounds group was less than that in the model group and the autophagy inhibitor group(P＜0.05).TTC staining showed that cerebral infarct foci were observed in the model group,Buqi Huoxue Compounds group,and autophagy inhibitor group,and the cerebral infarct volume in the Buqi Huoxue Compounds group was lower than that in the model group and the autophagy inhibitor group(P＜0.05).The results of hematoxylin-eosin staining in ischemic brain tissues showed that there were large gaps between nerve cells in the model group and cell arrangement was not neat,and cytoplasmic agglutination and pyknosis were observed.Immunohistochemical staining results showed that vascular endothelial growth factor was mostly expressed in neuronal cells,glial cells and capillary endothelium;basic fibroblast growth factor and brain-derived neurotrophic factor were mostly expressed in neuronal cells and glial cells;and there was no significant difference in the expression of vascular endothelial growth factor,basic fibroblast growth factor,and brain-derived neurotrophic factor among the four groups(P＞0.05).The results of western blot assay showed that compared with the sham operation group,Beclin1 protein expression was decreased(P＜0.05)and p62 protein expression was elevated(P＜0.05)in the model group;compared with the model group,Beclin1 protein expression was increased(P＜0.05)and p62 protein expression was reduced(P＜0.05)in the Buqi Huoxue Compounds group;compared with the Buqi Huoxue Compounds group,Beclin1 protein expression was decreased(P＜0.05)and p62 protein expression was elevated(P＜0.05)in the autophagy inhibitor group.To conclude,Buqi Huoxue Compounds attenuate cerebral ischemia-reperfusion injury in rats by promoting autophagy.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Background Multiple studies have shown a close relationship between changes in gut microbiota composition and obesity, and research results are influenced by factors such as race and geographical location, but there are few studies on children. Objective To analyze the diversity of gut microbiota related to obesity in a population of 2-6 years old, observe the distribution characteristics and species differences of gut microbiota between obese/overweight and normal weight groups, and explore the association betweenobese/overweight and gut microbiota diversity. Methods Fecal samples were collected from 74 children aged 2-6 years in Shanghai, including 18 obese/overweight individuals, 6 males and 12 females (male to female ratio of 1∶2), and 56 normal weight individuals, 18 males and 38 females (male to female ratio is nearly 1∶2). The 16S rDNA was extracted from bacteria in fecal samples, followed by PCR amplification, cDNA construction, and high-throughput sequencing. Naive Bayes algorithm was used to perform taxonomic analysis (phylum, class, order, family, genus, species) and community diversity analysis (Sobs index, Shannon index, Shannoneven index, Coverage index, PD index, and principal co-ordinates analysis) on representative sequences and abundance of amplicon sequence variants (ASV). Wilcoxon rank sum test, P-value multiple test correction, and analysis of similarities were used to test differences between the two groups to obtain information on the distribution characteristics and species differences of intestinal microbiota in children. Results Seventy-four fecal samples were sequenced, and the sequencing results were subjected to quality control and filtering. A total of 4905306 optimized sequences were obtained, resulting in 1860 ASVs. The diversity data analysis of ASVs generated 889 species annotation results at 8 taxonomic levels. The alpha diversity analysis showed that the richness (Sobs index), diversity (Shannon index), evenness (Shannoneven index), and phylogenetic diversity (PD index) of fecal community of the obese/overweight children were increased compared to those of the normal weight children, but there were no statistical differences between the two groups (P>0.05). The beta diversity analysis showed that there was little difference in the composition of microbial species between the two groups, and no significant clustering separation was observed. The results of species composition analysis at phylum, order, family, and genus levels of 74 samples showed a consistent core microbiota structure in the two groups of gut microbiota, but there were differences in microbiota composition. The differences in microbial community composition between the two groups were manifested at the taxonomic levels of order, family, and genus, among which phylum Firmicutes, order Erysipelotrichales, family Erysipelatocyclostridiaceae, genus Erysipelotrichaceae_ UCG-003 and genus Catenibacterium were significantly enriched in the obese/overweight group and contributed significantly to the phenotypic difference of obese/overweight [linear discriminant analysis (LDA)=3.72, P<0.01; LDA=3.29, P<0.05). Phylum Proteobacteria, order Enterobacterales, family Enterobacteriaceae, genus unclassified was significantly enriched in the normal weight group and contributed significantly to the phenotypic difference of normal body weight (LDA=3.93, P<0.05). Conclusion The richness and diversity of gut microbiota in obese/overweight children aged 2-6 years in Shanghai are increased, but there is no difference compared to normal weight children. There is a difference in the composition of gut microbiota between the obese/overweight group and the normal weight group.

ObjectiveTo explore the risk of different levels of pre-pregnancy obesity on trimester-specific thyroid dysfunction. MethodsQuestionnaire information， blood samples， and urine samples from a 2017 pregnancy cohort study in Shanghai， China were collected. A total of 2 455 pregnant women were included in the analysis. Pre-pregnancy BMI was calculated based on the height and self-reported pre-pregnancy weight. Serum TSH， total thyroxine （TT4）， free thyroxine （FT4）， total triiodothyronine （TT3）， free triiodothyronine （FT3）， thyroid globulin antibody（TgAb）， and Thyroid peroxidase antibody （TPOAb） were measured using the electrochemiluminescence method. Urine iodine levels were measured using the acid digestion method. Levels of thyroid function indexes of pregnant women with different degrees of obesity during pre-pregnancy were compared， and trimester-specific thyroid dysfunction was evaluated according to the reference range of trimester-specific thyroid hormone established by this cohort. Multivariate logistic regressions analysis was used to assess the correlation between pre-pregnancy obesity and trimester-specific thyroid dysfunction. ResultsAs the degree of obesity increased， maternal levels of FT3 and TT3 gradually increased during pregnancy （P<0.001， P=0.001）， while FT4 levels gradually decreased （P=0.001）. Multivariate logistic regression analysis showed that compared with the normal weight group， pregnant women who were overweight or obesity before pregnancy had a significantly higher risk of hypothyroxinemia （OR=3.85， 95%CI： 2.08‒7.14， P<0.001） and high TT3 （OR=2.78， 95%CI： 1.45‒5.26， P=0.002） during pregnancy. ConclusionPre-pregnancy overweight or obesity can increase the risk of thyroid dysfunction during pregnancy.

Objective To develop the assessment scale of proactive health behavior ability for the disabled elderly in nursing homes and to test its reliability and validity.Methods The first draft of the scale was formed by literature review,qualitative interviews and Delphi method.From December 2023 to March 2024,525 disabled elderly people from 9 nursing homes in Sichuan Province and Chongqing City were selected as the survey subjects,and item analysis and reliability and validity test were carried out on the scale.30 disabled elderly people were re-investigated after 2 weeks to calculate the retest reliability of the scale.Results The scale consisted of 4 dimensions and 27 items.Exploratory factor analysis extracted 4 common factors,with the cumulative vanance contribution rate of 65.992％,and confirmatory factor analysis showed that the modified model fitting index was within acceptable range.The content validity index at item level was 0.917-1.000,and that at scale level was 0.997.The Cronbach's α coefficient,test-retest reliability and split-half reliability of the total scale were 0.944,0.997 and 0.882,respectively.Conclusion The scale has good reliability and validity,and it can be used to evaluate the proactive health behavior ability of the disabled elderly in nursing homes.

This paper summarized the clinical experience of professor XUAN Guowei in treating non-specific vulvitis from spleen. He believes that the core pathological mechanism of this condition lies in spleen deficiency and dampness accumulation； in the acute phase， spleen deficiency is taken as the root cause and damp-heat toxins accumulated in the vulva as the key； in the chronic phase， spleen deficiency and dampness accumulation is the main pathogenesis， accompanied by kidney deficiency. In clinical practice， the basic method of fortifying spleen and eliminating dampness is used， and self-made Jianpi Shenshi Formula （健脾渗湿方） is recommended as the basic prescription. During the acute phase， the medicinals of clearing heat and resolving toxins are supplemented， while during the chronic phase， medicinals aims at fortifying the spleen and consolidating the kidneys， boosting qi and nourishing yin are added. Simultaneously， there is an emphasis on integrated treatment combining internal and external treatment， and both Chinese and western medicine， and he highlights the importance of daily prevention and care for patients. Additionally， external used Xiaoyan Zhiyang Cream （消炎止痒霜） is created.

Objective To analyze the short-term clinical efficacy and prognosis of one-stop transcatheter aortic valve replacement (TAVR)+percutaneous coronary intervention (PCI) in the treatment of aortic valve disease with coronary heart disease. Methods The clinical data of patients with aortic valve disease complicated with coronary heart disease who underwent one-stop TAVR+PCI treatment at the Department of Cardiovascular Surgery, the Second Hospital of Hebei Medical University from January 2018 to June 2023 were retrospective analyzed. The preoperative and postoperative clinical data were compared, and 1-month follow-up results were recorded. Results A total of 37 patients were enrolled, including 22 males and 15 females, with an average age of 69.14±6.47 years. Thirty-six patients recovered and were discharged after the surgery, and 1 (2.7%) patient died during the surgery. Self-expanding TAVR valves were implanted through the femoral artery in all patients. One coronary artery was opened by PCI in 35 (94.6%) patients, and two coronary arteries were opened by PCI in 2 (5.4%) patients. All PCI opened arteries had a stenosis>70%. During the postoperative hospitalization, the complications included pulmonary infection in 11 (30.6%) patients, severe pneumonia in 10 (27.8%) patients, liver function injury in 14 (38.9%) patients, renal function injury in 5 (13.9%) patients, cerebral infarction in 1 (2.8%) patient, atrial fibrillation in 1 (2.8%) patient, ventricular premature beats in 2 (5.6%) patients, atrioventricular block in 2 (5.6%) patients, and complete left bundle branch block in 5 (13.9%) patients. The median postoperative ventilation assistance time was 12.0 (0.0, 17.0) h, the ICU monitoring time was 1.0 (0.0, 2.0) d, and the postoperative hospitalization time was 5.0 (4.0, 7.0) d. There was a significant improvement in the New York Heart Association cardiac function grading after surgery (P<0.001). After surgery, there were 21 (58.3%) patients had minor perivalve leakage, 6 (16.7%) patients had minor to moderate perivalve leakage, and no moderate or above degree of perivalve leakage. After one month of postoperative follow-up, 36 patients showed significant improvement in heart function. There were no patients with recurrent acute coronary syndrome, re-PCI, or cardiovascular system disease related re-hospitalization. Conclusion The one-stop TAVR+PCI treatment for patients with aortic valve disease and coronary heart disease can obtain satisfactory short-term clinical efficacy, which is worth further trying and studying.

Consumptive thirst is widely discussed in Huangdi Neijing and it is classified as a"strange disease"in Suwen·Strange Diseases Treatise,which reflects the intractable nature of consumptive thirst.This paper explores and analyzes consumptive thirst based on the core concept in Huangdi Neijing.First,this paper approaches the subject through the use of image thinking method from Huangdi Neijing,recognizing that consumptive thirst can lead to changes in the internal climate of the human body.Then,guided by the theories of essence and qi,yin and yang,and the five elements in Huangdi Neijing,it deconstructs and analyzes the causes of these changes and the laws of qi transformation.It points out that the changing climate of consumptive thirst is characterized by"heat symptoms".The main cause of"heat symptoms"is spleen deficiency and excessive dampness,and its qi transformation law is the heat transformation of Shaoyin.The intractable nature of consumptive thirst is mainly reflected in the uncontrolled"heat symptoms"caused by the imbalance of the five elements.Based on the understanding of the heat symptoms of consumptive thirst,this paper proposes a treatment strategy for preventing the disease by resolving dampness and regulating the spleen,harmonizing kidney qi to prevent progression,and balancing yin and yang to treat chronic and recalcitrant conditions.The aim is to provide a reference for optimizing the treatment of consumptive thirst.

Objective To investigate the mechanism of inducing macrophage polarization induced by acupoint effect of electroacupuncture to promote the repair of acute skeletal muscle injury.Methods 45 SD rats were randomly divided into blank group,model group,electroacupuncture group(EA group),sodium chrominate group (DSCG group) and electroacupuncture+sodium chrominate group (hereinafter referred to as EA+DSCG group),with 9 rats in each group. The rats in the EA group and the EA+DSCG group were subjected to EA intervention at the right "Chengshan" (BL57) and "Yanglingquan"(GB34),with a frequency of 2 Hz/100 Hz. The gait changes of rats were recorded by animal gait analyzer. The morphological changes of the right gastrocnemius were observed by HE staining. The changes of mast cell aggregation and degranulation in local skin muscles of "chengshan" point were observed by toluidine blue staining. The expressions of Pax7,MyoD and skin mast cells and 5-HT in the right gastrocnemius were detected by immunofluorescence method. The positive expressions of CD68 and CD206 in right gastrocnemius macrophage was observed by immunohistochemical staining.Results Compared with blank group,the wiggle time of the right hind leg in model group and DSCG group increased,stride length decreased,HE staining showed inflammatory cell infiltration,myocyte enlargement,degeneration and necrosis. The degranulation rate of local skin mast cells in "Chengshan" (BL57) area increased,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD,CD68 and CD206 increased (P<0.05). Compared with model group,the wiggle time of the right hind leg in EA group and EA+DSCG group decreased,stride length increased,HE staining showed that inflammatory cell infiltration was reduced,muscle cells were uniform in size and arranged neatly. Mast cell degranulation rate increased significantly in EA group,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased (P<0.05). Compared with EA+DSCG group,the degranulation rate of mast cells and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased in EA group (P<0.05). Conclusion EA "Chengshan" (BL57) and "Yanglingquan" (GB34) can stimulate acupuncture points to locally induce mast cell degranulation,promote the polarization of macrophages,and then activate muscle satellite cells to play the regulatory process of repairing skeletal muscle injury.