Latest ArticlesLiver 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.
Objective To investigate the correlation between high-density lipoprotein cholesterol (HDL-C) levels and the risk of thyroid carcinoma in the population undergoing surgery for thyroid nodules. Methods The clinical data of 3996 patients who underwent thyroid surgery at the First Medical Center of PLA General Hospital from January 2016 to December 2020 were collected for retrospective analysis, 2846(71.2%) were females and 1150(28.8%) were males, including 3414(85.4%) thyroid carcinoma cases and 582 benign nodules (14.6%). The patients were divided into quintiles groups (Q1-Q5) according to HDL-C level from low to high. The clinical data characteristics of the five groups were compared, and multivariate logistic regression analysis was used to analyze the correlation between HDL-C level and thyroid carcinoma risk. A restricted cubic spline logistic regression model was established to analyze its dose-response relationship. Results As the level of HDL-C climbed from the first to the fifth quintile(Q1-Q5), the proportion of women in the study groups increased, whereas the proportions of thyroid carcinoma, body mass index(BMI), triglyceride levels and fasting blood glucose levels reduced significantly (P<0.05). After adjusting for confounding factors such as age, gender, BMI, thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and free triiodothyronine/free thyroxine (FT3/FT4) levels, the level of HDL-C remained a significant independent factor for thyroid carcinoma (OR=0.52, 95%CI 0.37-0.72, P<0.001). The trend test revealed statistically significant variations (P for trend <0.001). The E-value analysis indicated E=2.119. Compared with the study population with both TgAb and TPOAb being negative (OR=0.41, 95%CI 0.28-0.60, P<0.001) or positive for either antibody (OR=1.12, 95%CI 0.51-2.46, P=0.777), the correlation between HDL-C and thyroid cancer risk was stronger in patients with both TgAb and TPOAb being negative (P for interaction=0.014). A restricted cubic spline analysis revealed no nonlinear association between HDL-C levels and the risk of thyroid carcinoma in either men or women. Conclusion High HDL-C levels are associated with a lower risk of thyroid carcinoma in the population receiving surgery for thyroid nodules, particularly in patients with negative TgAb and TPOAb.
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 analyze the mechanism of skeletal muscle atrophy in mice caused by Opg gene knockout based on metabolomics. Methods Five 3-month-old wild-type C57BL/6 male mice and five 3-month-old male Opg gene knockout mice were set as wild-type group and gene knockout group, respectively. Left femur and gastrocnemius muscle of mice were taken for evaluating the bone microstructure with micro-CT scanning and observing the morphological changes of gastrocnemius muscle by HE staining; The spermidine content in gastrocnemius muscle was detected by immunofluorescence staining. Ten 3-month-old male wild-type C57BL/6 mice, ten 3-month-old male Opg knockout mice and ten 18-month-old male wild-type C57BL/6 mice were set as young wild-type (WT-Y) group, young knockout (OPG-Y) group and old wild-type (WT-O) group, which were used for gastrocnemius metabolomics analysis. Results Compared with wild-type mice, Opg knockout mice showed fewer bone trabeculae, decreased bone density, cortical bone structure was destroyed, the weight of gastrocnemius muscle and the cross sectional area of gastrocnemius fiber were decreased (P<0.05). Metabolomics analysis showed that, compared with WT-Y mice, metabolites involved in glucose, phospholipid and amino acid metabolism, such as glucose-1-phosphate, D-glucose-1, 6-bisphosphate, multiple amino acids, choline, carnitine etc. were significantly up-regulated in WT-O mice, while γ-aminobutyric acid, spermidine, pantothenate etc. were significantly down-regulated. Compared with WT-Y mice, metabolites such as choline, β-glycerophosphate, azelaic acid etc. were up-regulated in OPG-Y mice, while other metabolites such as spermidine, pantothenate, N6, N6, N6-trimethyl-lysine etc. were significantly down-regulated, which were mainly involved in amino acid metabolism. The validation results of metabolomics analysis suggested that the content of spermidine in gastrocnemius of Opg knockout mice was significantly lower than that of WT-Y mice (P<0.01). Conclusion Opg knockout may regulate the levels of metabolites such as spermidine and regulate the level of metabolites such as spermidine and pantothenic acid through amino acid metabolism and other pathways, which cause skeletal muscle atrophy.
Objective To investigate the correlation between serum triglyceride (TG) levels and papillary thyroid carcinoma (PTC) in patients undergoing thyroid nodule surgery. Methods A retrospective analysis was conducted with the clinical data of 3340 patients with thyroid nodular disease [940 males (28.1%) and 2400 females (71.9%) with age of (44.5±11.4) years]who underwent thyroid nodule surgery and had complete operative blood lipid data in the First Medical Center of PLA General Hospital from January 2016 to December 2020. Based on the postoperative pathological condition, all the patients were divided into PTC group (2867 cases) and benign thyroid nodules group (473 cases). Analyze the general data of the two groups of patients using logistic regression to analyze the correlation between serum TG levels and the risk of PTC, and analyze the risk of PTC in age, gender, BMI, and thyroid autoantibody subgroups. Results Compared with benign nodules group, the serum TG levels of patients in PTC group were significantly higher [1.2(0.8, 1.7) vs. 1.1(0.8, 1.5), P<0.001]. Multivariate binary logistic regression analysis revealed that serum TG levels were associated with an increased risk of PTC disease (adjusted OR=3.067, 95%CI 1.839-5.116, P<0.001). Triglyceride levels were categorized into quartiles, with the lowest quartile serving as a reference. The relative risk for the highest quartile of triglycerides in PTC patients was 2.142(95%CI 1.548-2.965, P<0.001), and this association persisted even when serum triglycerides were within the normal reference range (adjusted OR=3.244, 95%CI 1.440-7.307, P=0.005). Subgroup analysis demonstrated that serum TG were associated with an increased risk of PTC only in patients with negative thyroid autoantibodies and a BMI<28 kg/m2 (P<0.05). Moreover, the risk of PTC was more pronounced in patients under 45 years of age compared with those aged 45 years and older (P for interaction=0.043). Conclusion Elevated serum triglyceride levels were associated with an increased risk of PTC in patients with negative thyroid autoantibodies and BMI<28 kg/m2.
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.
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 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 effect of resveratrol (Res) on microglia function after intracerebral hemorrhage (ICH) and its possible mechanism. Methods (1) Animal experiment: 27 SD rats (12-week-old) were randomly divided into 3 groups (9 each): control group, ICH group and Res group; each group was randomly divided into three subgroups (3 each) at 6 h,24 h and 72 h after operation. Rats in ICH group were modeled by autologous blood modeling method, while in control group were only injected with needles without autologous blood injection. Rats in Res group were intraperitoneally injected with 50 mg/(kg.d)resveratrol on the basis of ICH group, and 2% dimethyl sulfoxide (DMSO) solvent of the same volume were injected in control group and ICH group. 6 h, 24 h and 72 h after successful modeling, the corresponding rats were subjected to modified neurological severity score (mNSS). Then the rats in each subgroup were sacrificed and their brain tissues were taken from the same area and embedded in wax blocks. The expression of TRL4, CD36, HO-1 and Nrf2 protein in rat brain tissue was observed by tissue section, HE staining,Nissl staining, TUNEL staining and immunofluorescence method. (2) Cell experiment: BV2 mouse microglia cells were divided into control group, Fe2+ group (FeSO4 10 μmol/L) and Fe2++low dose resveratrol (25 μmol/L) group and Fe2++high dose resveratrol(50 μmol/L) group. The expression levels of TLR4, CD36, Nrf2, p-Nrf2, and HO-1 proteins were detected by Western blotting after incubation for 24 h and 72 h, respectively, and the localization of Nrf2 protein was observed by cell immunofluorescence. Results (1) mNSS score indicated that rats in ICH group had obvious neurological dysfunction while normal in control group. mNSS score of rats was significantly higher in ICH group than in control group (P<0.01). As time went by 24 h or 72 h, mNSS score of rats reduced significantly in Res group than in ICH group (P<0.05, P<0.01). HE staining of rat brain tissue indicated that increased infiltration of red blood cells and inflammatory cells were in ICH group, and the infiltration of red blood cells and inflammatory cells in the brain tissue of rats in Res group was improved compared with those in ICH group. Nissl staining of rat brain tissue showed that, compared with the control group, the dissolution of nissl corpuscles in brain tissue of ICH group increased, and in Res group decreased. TUNEL staining of rat brain tissue showed that the neurocyte apoptosis index in brain tissue of rats in ICH group increased significantly compared with that in control group (P<0.05), and it was significantly lower in Res group compared with ICH group (P<0.05). The immunofluorescence of proteins indicated that the expressions of TLR4, CD36, Nrf2 and HO-1 protein in rats'brain tissue in ICH group increased significantly compared with rats in control group (P<0.05). Compared with rats in ICH group,the expression of TLR4 protein in brain tissue of the rats in Res group decreased at the same time point (P<0.05), while the protein expressions of CD36, Nrf2 and HO-1 increased significantly (P<0.05). (2) Compared with the control group, the relative expression of TLR4, CD36 and HO-1 protein in BV2 cells of Fe2+ group increased (P<0.05), the expressions of Nrf2 and p-Nrf2 increased at 72 h (P<0.05), the expression of Nrf2 protein in the nucleus increased (P<0.01); Compared with the Fe2+ group, the expression of TLR4 in the low dose group of Fe2++Res and the high dose group of Fe2++Res decreased (P<0.001), and the expression of CD36,HO-1, Nrf2, p-Nrf2 and nuclear Nrf2 protein increased (P<0.05). Conclusions Intraperitoneal injection of resveratrol can improve the neurological function of rats after ICH. The microglia activated by Fe2+ within 72 hours after intracerebral hemorrhage mainly showed pro-inflammatory function. Resveratrol may regulate Nrf2/HO-1 signal pathway and promote the transformation of microglia function to anti-inflammatory after ICH.
Objective To explore the effect of endoscopic radical thyroidectomy combined with parathyroid autotransplantation on the recovery of postoperative parathyroid function. Methods The clinical data of 323 patients undergoing endoscopic radical resection of thyroid carcinoma in the General Surgery Department of Gansu Provincial People's Hospital from January 2019 to April 2021 were retrospectively analyzed and divided into transplant group (n=171) and non-transplant group(n=152) according to whether combined with selective parathyroid. The incidence of circulating parathyroid hormone (PTH),Ca2+ concentration and hypoparathyroidism were recorded before surgery and 1 day, 1 week, 1 month, 3 months, 6 months and 12 months after surgery in both groups, and the PTH concentration in the elbow fossa veins of both arms were collected in the transplant patients. Risk factors for hypoparathyroidism after thyroid surgery were analyzed using logistic regression. Results The incidence of transient hypoparathyroidism was higher, while of permanent hypoparathyroidism was lower in transplant group than in non-transplant group (33.33% vs. 23.03%; 0.58% vs. 5.26%), the differences were significant (P=0.007). The PTH concentrations were significantly higher in transplant group than in non-transplant group from 1 week to 12 months after surgery with statistically significant difference (P<0.001). The PTH concentration in vein of transplant side cubital fossa was significantly higher from 1 week to 12 months after surgery in transplant group than in non-transplant group, and the differences were statistically significant(P<0.001). Twelve months after surgery, PTH secretion function in transplant group and non-transplant group had recovered to 85.42% and 67.60% of preoperative baseline, respectively. Univariate logistic regression analysis showed that transplantation and Hashimoto's thyroiditis were the risk factors for temporary hypoparathyroidism after thyroid surgery (OR=1.671, 95%CI 1.020-2.738,P=0.041; OR=1.925, 95%CI 1.138-3.259, P=0.015), and transplantation was a protective factor for permanent hypoparathyroidism(OR=0.106, 95%CI 0.013-0.857, P=0.035). Multi-factor logistic regression analysis showed that transplantation and Hashimoto's thyroiditis were the risk factors for temporary hypoparathyroidism (OR=1.736, 95%CI 1.044-2.887, P=0.034; OR=1.903, 95%CI 1.111-3.258, P=0.019), and transplantation was a protective factor for permanent hypoparathyroidism (OR=0.101, 95%CI 0.012-0.839, P=0.034). Conclusion In endoscopic radical resection of thyroid carcinoma, parathyroid autotransplantation is an effective strategy to prevent permanent hypoparathyroidism, but can also lead to short-term postoperative hypoparathyroidism. As far as possible, selective transplantation of the inferior pole parathyroid glands with intraoperative damage or poor blood supply, based on in situ preservation of the superior pole parathyroid glands, is more conducive to recovery of postoperative parathyroid function.