Objective To evaluate the usability of tablet-based digital complex figure test (dCFT) software on assessment of drawing strategies of patients with amnestic mild cognitive impairment (aMCI). Methods A total of 64 patients treated in a hospital from Nov. 2020 to Nov. 2021 were selected, including 26 cognitively normal people (control group) and 38 aMCI patients(aMCI group). All subjects underwent standardized neuropsychological assessments, including the mini-mental state examination(MMSE), the montreal cognitive assessment (MoCA), the Rey–Osterrieth Complex Figure (ROCF) test, and other cognitive domain scales. And then use the dCFT (including copying and recall) developed by our team to collect drawing parameters, such as stroke length, time, speed and number. The Pearson correlation coefficient was used to evaluate the correlation between the original and simplified ROCF test scores, and partial correlation used to analyze the correlation between the dCFT parameters and the comprehensive scores of each cognitive domain. Results (1) In the copying test, all dCFT parameters had no statistically significant between the two groups (P>0.05). In the immediate recall test, the total thinking time and element delay time in aMCI group were significantly longer than those in the control group [27.15(21.49, 33.94) vs. 21.85(18.26, 24.81), 1.99(1.36, 3.62) vs.1.32(1.03, 1.99), P<0.05]. In the delayed recall test, the transition time of short and long stroke sequence, total thinking time, total completion time, first thinking time and element delay time of the aMCI group were significantly higher than those of control group [1.89(1.12, 3.93) vs. 1.19(0.42, 2.41), 23.94(18.86, 36.87) vs. 19.93(16.59, 23.00), 40.30(34.83, 56.21) vs. 34.52(29.96, 42.15), 7.92(6.20, 9.83) vs. 5.92(5.16, 8.04), 1.63(1.25, 2.47) vs. 1.08(0.83, 1.55), P<0.05]. The first 5 stroke ratios (%), speed of the longest stroke (cm/s) and strokes per minute of aMCI group were significantly lower than those of control group [60(40, 80) vs. 80(60, 100), 4.65(3.53, 6.07) vs. 6.00(4.54, 7.13), 21(18, 25) vs. 26(21, 27), P<0.05]. Other dCFT parameters had no statistically significance between the two groups (P>0.05). (2) Correlation analysis showed that the transition time was negatively correlated with attention and executive function (r=–0.292, r=–0.275, P<0.05); the speed of the longest stroke was positively correlated with the executive function (r=0.302, P<0.05); the total thinking time was negatively correlated with memory, attention, executive function and visuospatial ability (r=–0.26, r=–0.408, r=–0.448, r=–0.264, P<0.05); the total completion time was negatively correlated with attention, executive function and visuospatial ability (r=–0.342, r=–0.429, r=–0.273, P<0.05); the first stroke latency was negatively correlated with memory and visuospatial ability (r=–0.365, r=–0.407, P<0.01); the average element latency was negatively correlated with memory and attention (r=–0.377, r=–0.33, P<0.01); the strokes per minute was positively correlated with memory, attention, executive function and visuospatial ability (r=0.326, r=0.311, r=0.376, r=0.263, P<0.05). Conclusions Visuospatial memory impairment of aMCI patients was presented in 3-minute recall test of the complex figure test, and their drawing strategy was acceptable. But after 20 minutes, the memory and the organization strategy of drawing were significantly affected. Visual perception is not significantly impaired in the process. The dCFT software is a convenient, objective assessment tool for aMCI.

Objective To investigate the regulatory effect and molecular mechanism of circAPLP2 on invasion and metastasis of colorectal cancer cell SW480. Methods The online database Starbase was used to predict the binding sites of circAPLP2 and miR-497-5p, and TargetScan was used to predict the binding sites of miR-497-5p and FGFR1. The relative expression levels of circAPLP2 and miR-497-5p in LoVo, DLD1, SW480, SW620, Caco-2 and HCoEpiC cells were detected by qRT-PCR, and the relative expression level of FGFR1 protein was detected by Western blotting. SW480 cells were taken and set up as follows:(1) siNC group (transfected with siControl) and sicircAPLP2 group (transfected with sicircAPLP2), the expressions of circAPLP2, miR-497-5p, FGFR1 mRNA were detected by qRT-PCR, and the expression of FGFR1 protein was detected by Western blotting.(2) Vector group (transfected with empty plasmid) and circAPLP2 group (transfected with circAPLP2 overexpression plasmid), the expressions of miR-497-5p and FGFR1 mRNA were detected by qRT-PCR, and the expression of FGFR1 protein was detected by Western blotting. (3) siNC group (transfected with siControl), sicircAPLP2 group (transfected with sicircAPLP2) and sicircAPLP2+miR-497-5p inhibitor group (transfected with sicircAPLP2 and miR-497-5p inhibitor), the cell invasion was detected by Transwell, the cell migration was detected by scratch test, and the expressions of EMT marker proteins (E-cadherin, Twist1, N-cadherin and Vimentin) were detected by Western blotting. (4) NC miRNA group (transfected with NC-miRNA) and miR-497-5p mimics group (transfected with miR-497-5p mimics), or NC-inhibitor group (transfected with NC-inhibitor) and miR-497-5p inhibitor group (transfected with miR-497-5p inhibitor), the expression of FGFR1 was detected by qRT-PCR and Western blotting.(5) pcDNA-Control group (transfected with pcDNA-Control) and pcDNA-FGFR1 group (transfected with pcDNA-FGFR1), the expression of FGFR1 protein was detected by Western blotting. (6) NC-miRNA group (transfected with negative control), miR-497-5p mimics group (transfected with miR-497-5p mimics) and miR-497-5p mimics+pcDNA-FGFR1 group (co transfected with miR-497-5p mimics and pcDNA-FGFR1), the cell invasion, migration and the expression of FGFR1 and EMT marker proteins(E-cadherin, Twist1, N-cadherin, Vimentin) were detected by Transwell, scratch test or Western blotting. The circAPLP2-WT or circAPLP2-MT report plasmid was co-transfected with NC-miRNA or miR-497-5p mimics respectively for 48 h in SW480 cells, and the FGFR1-WT or FGFR1-MT report plasmid was co-transfected with miR-497-5p mimics and circAPLP2 respectively for 48 h in SW480 cells, and the luciferase activity was detected by the luciferase reporter gene detection system. Results The analysis results by Starbase and TargetScan showed that binding sites existed between circAPLP2 and miR-497-5p, and between miR-497-5p and FGFR1. Compared with human colon epithelial cell HCoEpiC, the relative expression level of circAPLP2 in colorectal cancer cells LoVo, DLD1, SW480, SW620 and Caco-2 increased significantly, while of miR-497-5p significantly decreased, and the relative expression level of FGFR1 protein significantly increased (P<0.05). After knocking down the expression of circAPLP2, compared with siCN group, the number of invasive cells in sicircAPLP2 group decreased (P<0.001), and the cell healing rate of scratches decreased (P<0.001), the expression of E-cadherin protein increased, and the protein expressions of Twist1, N-cadherin and Vimentin decreased (P<0.05). The results of dual luciferase reporter assay showed that miR-497-5p mimics decreased circAPLP2-MT luciferase activity significantly (P<0.001); MiR-497-5p inhibitor reverses the inhibitory effect of sicircAPLP2 on EMT, migration and invasion of colorectal cancer cells, as the number of invasive cells increased (P<0.001), the scratch healing rate increased (P<0.01), the expression of E-cadherin protein decreased, and the expression of Twist1, N-cadherin, and Vimentin protein increased (P<0.05). Dual luciferase reporter assay results showed that miR-497-5p mimics significantly reduced FGFR1-MT luciferase activity (P<0.001). Over-expression of FGFR1 reversed the inhibition of miR-497-5p overexpression on colorectal cancer cell migration and invasion, manifested as increased number of invasive cells (P<0.001), increased scratch healing rate (P<0.01), decreased expression of E-cadherin, increased expressions of N-cadherin, Twist1 and Vimentin (P<0.05). Conclusion The expression level of circAPLP2 increases in colorectal cancer cells, it may promote the expression of FGFR1 through competitive combination with miR-497-5p, thus promoting EMT, invasion and migration of colorectal cancer cells.

Objective To investigate the effect and potential mechanism of Taohong Siwu decoction(THD) on paclitaxel-induced peripheral nerve injury in rat. Methods Twenty-four female SD rats were randomly divided into control group, model group, THD low-dose group and THD high-dos group (6 each). Rats in control group were given saline of the same volume, while paclitaxel (8 mg/kg) was slowly injected intraperitoneally into rats in other three groups on the 1, 3, 5, and 7th day for 4 times. Rats with mechanical withdrawal threshold under 4 g indicated model success. The THD low-dose group and THD high-dose group was given 1 g/ml or 2 g/ml of THD 2 times/d, for 4 weeks. The threshold of mechanical stimulation, cold and hot stimulation to rats was detected after administration. The pathological morphology of sciatic nerve was observed by HE staining.The contents of inflammatory factor Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), thiobarbituric acid reactive substances (TBARS) and L-Glutathione (GSH) in the sciatic nerve were measured with automatic biochemical analyzer.The relative contents of myelination pieces were determined by red oil O staining and expression level of autophagy associated proteins microtubule-associated protein 1 light chain3-I (LC3-I), LC3-Ⅱ, and Beclin1 were detected by Western blotting. Results Compared with control group, rats in model group showed lower threshold to mechanical stimulation and lower sensitivity to hot and cold stimulation (P<0.05), expression levels of IL-6, TNF-α and TRABS elevated (P<0.05), while GSH levels decreased (P<0.05). HE staining showed tissue injury, atrophy, inflammatory infiltration, and myelination pieces increased significantly and expression of autophagy associated protein LC3-I, LC3-Ⅱand Beclin1 reduced (P<0.05). The results of THD low-dose group and THD high-dose group showed that the response of rats to mechanical stimulation, hot and cold stimulation was obviously improved (P<0.05), levels of IL-6, TNF-α and TRABS significantly decreased (P<0.05), while level of antioxidant GSH significantly elevated (P<0.05). Compared with THD low-dose group, rats in THD high-dose group showed elevated threshold to mechanical stimulation and more sensitive to mechanical stimulation, hot and cold stimulation (P<0.05), myelination pieces decreased significantly (P<0.05) and expression of autophagy associated protein LC3-I, LC3-Ⅱand Beclin1 increased (P<0.05). Conclusion Taohong Siwu decoction can alleviate rat peripheral nerve injury caused by paclitaxel, and its mechanism may be related to reducing inflammatory reaction and inducing autophagy to remove damaged debris.

Objective To investigate the effects of mesenchymal stem cells (MSCs) on inflammatory factors and T-lymphocyte subsets in naturally aged sepsis rats. Methods Ninety naturally aged SD rats (21 months old) were divided into 3 groups according to the random number table method: 36 rats in the model group, 36 rats in the treatment group, and 18 rats in the sham group. In each group, animals were then randomly divided equally into three sub-groups. The rats were severed and executed after 6-h, 24-h, and 72-h anesthesia for modeling or treatment, respectively. The sepsis model was established by the cecum ligation perforation (CLP) method. The sham group was operated as the model group, except that the cecum ligation and perforation method was not used. After 1-hour of modeling, the rats in the treatment group were injected with umbilical cord MSCs through the tail vein, and the rats in the model group and the sham group were injected with the same volume of saline through the tail vein. The 72-hour survival rate of rats in each group was observed, and the levels of interleukin (IL)-1β, IL-6, IL-10, IL-17A, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β were measured by Aimplex method. The spleens of rats in each group were stained with TUNEL and the apoptosis of spleen lymphocytes was observed by laser confocal microscopy; the ratio of CD4⁺/CD8⁺ T cells in each group was analyzed by flow cytometry. Results The rats in the sham group showed no abnormalities during the observation period, and the survival rate at 72-hour after surgery was 100.00%. The rats in the model group showed symptoms such as vertical hair, loss of appetite, and depression after surgery, while these symptoms were improved in the treated rats, and the survival rate at 72-hour after CLP surgery was significantly higher in the treatment group than in the model group (66.67% vs.41.67%, P<0.01). Compared with the sham group, the model group showed increased levels of IL-1β, IL-6, and IL-17A, blurred spleen structure, increased proportion of apoptotic lymphocytes, and decreased proportion of CD4⁺/CD8⁺ T lymphocytes in peripheral blood and spleen, all with statistically significant differences (P<0.05). Compared with the model group, the treatment group showed reduced levels of IL-1β, IL-6 and IL-17A, increased levels of IL-10, clear spleen structure, significantly reduced lymphocyte apoptosis, and increased proportions of CD4⁺/CD8⁺ T lymphocytes in peripheral blood and spleen, all with statistically significant differences (P<0.05). Conclusions MSCs were able to significantly improve the survival rate of naturally aged sepsis rats, suppress excessive inflammatory responses, reduce lymphocyte apoptosis, and improve the immune function of the body, thus exerting a protective effect on naturally aged sepsis rats.

Objective To investigate the risk factors of lymph node metastasis in papillary thyroid carcinoma (PTC)patients who had thyroid nodule operation. Methods The clinical data of 4742 patients, who had surgical treatment for thyroid nodule from January 2016 to December 2020 in the First Medical Center of Chinese PLA General Hospital, were collected for retrospective study. The pathologic specimens of thyroid and lymph nodes of all the patients were retained during surgery. The patients were divided into metastasis group (n=2407) and non-metastasis group (n=2335) according to lymph node metastasis. The differences of age, sex, body mass index, thyroid stimulating hormone (TSH) value, tumor diameter, capsule invasion, and range of glandular lobe involvement were analyzed between the two groups. The independent risk factors for lymph node metastasis of papillary thyroid carcinoma were evaluated by logistic regression, and multivariate regression analysis were performed based on tumor diameter dividing into subgroups of small and non-small cancers. Results In 4742 patients with PTC, the incidence of cervical lymph node metastasis was 50.8% (2407 cases). Multivariate analysis showed that male, age <45 years, increased tumor diameter, external thyroid extension (ETE), and multiple tumors were independent risk factors for cervical lymph node metastasis(P<0.001). BMI (P=0.369), TSH level (P=0.246) and Hashimoto thyroiditis were not associated risk factors. Subgroup analysis showed that unilateral multiple foci was an independent risk factor for lymph node metastasis in non-microcarcinomas (OR=1.67, 95%CI 1.20-2.31, P=0.002), and ETE in microcarcinomas was also a risk factor for lymph node metastasis (OR=1.58, 95%CI 1.27-1.96, P<0.001). Conclusion Male, <45 years old, tumor size ≥9.5 mm, ETE and multiple tumors are independent risk factors for cervical lymph node metastasis in PTC patients.

Objectives To understand the natural course of infection complications in elderly patients with tunnel-cuffed catheter (TCC) blood purification; and analyze the prognostic significance of blood routine test parameters detected before catheterization. Methods Collect 2430 patients who underwent blood purification treatment at the First Medical Center of the Chinese PLA General Hospital from January 2008 to January 2023, and follow up the patients who used TCC and had blood routine tests 24 hours before catheterization. Analyze the natural course of infection complications after TCC; Using all-cause death as the endpoint, Kendall correlation analysis was used to investigate the relationship between clinical data of first infection after TCC and prognosis. The nested case-control study was used to match the case group with the control group according to the ratio of hypertension and diabetes 1:1. The first infection within 6 months of TCC was taken as case group (n=34), and the first infection after 6 months of TCC was taken as control group (n=34). The risk factors related to the first infection within 6 months of TCC were analyzed by logistic regression. Validate the results of nested case-control studies across the entire group of patients and analyze the value of mean platelet volume (MPV) before catheterization in predicting the prognosis of first-time infections. Results A total of 77 patients were followed up, aged (78.4±7.3) years, with a median follow-up time of 28.0(13.8-70.5) months. After the first infection, 32 died and 45 survived. Compared with first-time infected survivors, deceased patients had a higher age and lower catheter age (P<0.05). The first infection within 6 months of TCC is positively correlated with death (r=0.336, P=0.003), and the cumulative survival rate is significantly lower than that in infected patients after 6 months of TCC (P<0.001). The results of a nested case-control study showed that the MPV of infected group within 6 months of TCC was significantly higher than that in control group [(10.64±1.05) fl vs. (9.89±0.80) fl, P=0.001]. Logistic regression analysis showed that the risk of infection was 3.222 times higher in high MPV group compared with control group. In the entire group of 77 cases, it was confirmed that high MPV values were associated with the occurrence of first infection within 6 months of TCC (P=0.037). Conclusions First infection within 6 months after TCC catheterization is associated with death; Patients with high MPV values before catheterization have a significantly increased risk of first infection within 6 months after TCC. The MPV level before catheterization may indicate a poor prognosis for infected individuals after TCC, and this indicator may be a personalized decision-making reference for TCC.

Liver fibrosis is a response to chronic liver injury caused by a variety of factors, such as alcohol consumption, viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD) and cholestatic liver disease. The combined effect of all these factors on the liver is to produce chronic inflammation leading to an abnormal wound-healing response. Mesenchymal stem cells (MSCs) are pluripotent stem cells that are able to implant into target tissues and secrete a variety of factors that can alter or improve the function of damaged tissues. Stem cells have the advantages of self-renewal, pluripotent differentiation and low immunogenicity. Due to their differentiation potential and paracrine characteristics, MSCs are the key for repair. This review focuses on the mechanism and progress of MSCs and their modifiers in liver fibrosis.

Acute respiratory distress syndrome (ARDS) refers to acute diffuse lung injury and subsequent acute respiratory failure caused by various intrapulmonary and extrapulmonary pathogenic factors, with respiratory distress and refractory hypoxemia as clinical features. At present, the "standardized" mechanical ventilation for ARDS patients is a lung protective ventilation strategy with low tidal volume and high positive end-expiratory pressure. However, the results are often unsatisfactory, and most related clinical studies have ended up unsuccessfully. Because of the high heterogeneity of ARDS, accurate classification and individualized treatment are very important. In this paper, we reviewed the phenotypes of ARDS from the perspectives of etiology, onset time, disease severity, inflammation level, imaging characteristics pathology, etc., and preliminarily explained the ARDS phenotype associated with COVID-19, and summarized the individualized treatment strategies for ARDS with different phenotypes, hoping to provide evidence for the individualized and precise treatment of ARDS.

Objective To investigate the effect of early injection of umbilical cord mesenchymal stem cells (UC-MSCs)on the progression of diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM) mice and its mechanism. Methods Twenty 5-week-old male db/db mice were used to establish T2DM model and randomly divided into stem cell treatment group(MSCs group, n=10) and T2DM group (DM group, n=10); In addition, age-matched db/m mice were set as normal control group(NC group, n=10). Human UC-MSCs (1×10⁶/0.2 ml saline) were infused into the tail vein of mice in MSCs group for 6 weeks,while the same volume of saline was infused into the tail vein of mice in NC and T2DM groups once a week for 6 consecutive times. Blood glucose and body weight of mice in each group were monitored weekly. At the end of the sixth treatment, the mice in each group were killed by heart perfusion, and the blood and kidney tissues were collected for biochemical and histopathological examination. Western blotting was used to detect the expression of silent information regulator 2 homolog 1 (SIRT1) and Claudin-1,and immunohistochemistry was used to detect the expression of SIRT1, Claudin-1, type 1 collagen (Col Ⅰ) and Col Ⅳ. The morphology of glomeruli was observed by electron microscope. HK-2 cells in logarithmic growth phase were divided into control group, high glucose induced model group (HG group), high glucose induced siRNA group (HG+siRNA group), MSC groups(HG+MSC group) and SIRT-1 siRNA group (HG+MSC+siRNA group). The expression levels of apoptosis-related proteins were detected by Western blotting. Results After the sixth treatment, compared with NC group [(7.66±0.37) mmol/L], the levels of blood glucose increased significantly (P<0.01) in T2DM group and MSCS group [(32.54±0.36) mmol/L, (29.74±1.04)respectively]; Compared with T2DM group, the level of blood glucose in MSCs group decreased significantly (P<0.05).Pathological results showed that compared with NC group, glomerular sclerosis, diffuse thickening of basement membrane and renal interstitial fibrosis were significantly increased in T2DM group; compared with T2DM group, glomerular sclerosis, deposition of mesangial extracellular matrix and renal interstitial fibrosis were alleviated in MSCs group. The results of Western blotting and immunohistochemistry showed that compared with T2DM group, the expression level of SIRT1 protein in MSCs group increased significantly (P<0.01), the expression of Claudin-1 protein decreased significantly (P<0.01), and of α-smooth muscle actin (α-SMA)protein decreased significantly in MSCs group (P<0.05). In addition, the immunohistochemical results showed that the percentage of Col Ⅰ and Col Ⅳ positive area in MSCs group was significantly lower than that in T2DM group (P<0.01). Compared with NC group, T2DM group showed marked destruction of glomerular filtration barrier, diffuse thickening of basement membrane, and extensive fusion and disappearance of foot processes. Compared with T2DM group, the structure of glomerular foot process in MSCs group was regular and complete. Western blotting results showed that SIRT-1 protein content was significantly lower in HG group than that in control group (P<0.01), while apoptosis-related Cytochrome-C protein contents were significantly higher in HG group than that in control group (P<0.01). Compared with HG group, the protein content of SIRT-1 in HG+MSC group was significantly higher (P<0.01), and the content of apoptosis-related Bax and Cytochrome-C protein decreased significantly (P<0.01).Compared with HG+MSC group, the protein content of SIRT-1 in HG+MSC+siRNA group was significantly decreased (P<0.01),while the protein content of apoptosis-related Bax and Cytochrome-C increased significantly (P<0.01). Conclusion UC-MSCs treatment may play a protective role for kidney of T2DM mice and delay the development of DN by up-regulating the expression of SIRT1 and down-regulating the expression of Claudin-1.

Ischemic heart disease (IHD) is one of the diseases with the highest mortality in the world, which endangers human health for a long term. Reperfusion, the preferred treatment strategy, can lead to myocardial deterioration and accelerate injury, known as myocardial ischemia-reperfusion injury (MIRI), which seriously affects the clinical efficacy and prognosis of patients. At present, the prevention and treatment of MIRI is still an unsolved clinical problem. Numerous studies have shown that adaptor protein p66Shc plays an important regulatory role in the occurrence and development of various diseases, including MIRI.The mechanism of adaptor protein p66Shc involved in oxidative stress, inflammatory response and vascular endothelial function in MIRI, and the relevant treatment strategies targeting p66Shc were reviewed in present paper in order to provide a reference for further research on prevention and treatment of MIRI.