A novel surgical scheme for hepatectomy in hepatocellular carcinoma patients with clinically significant portal hypertension.

OBJECTIVE: Clinically significant portal hypertension (CSPH) seriously affects the feasibility and safety of surgical treatment for hepatocellular carcinoma (HCC) patients. The aim of this study was to establish a new surgical scheme defining risk classification of post-hepatectomy liver failure (PHLF) to facilitate the surgical decision-making and identify suitable candidates for individual hepatectomy among HCC patients with CSPH. BACKGROUNDS: Hepatectomy is the preferred treatment for HCC. Surgeons must maintain a balance between the expected oncological outcomes of HCC removal and short-term risks of severe PHLF and morbidity. CSPH aggravates liver decompensation and increases the risk of severe PHLF thus complicating hepatectomy for HCC. METHODS: Multivariate logistic regression and stochastic forest algorithm were performed, then the independent risk factors of severe PHLF were included in a nomogram to determine the risk of severe PHLF. Further, a conditional inference tree (CTREE) through recursive partitioning analysis validated supplement the misdiagnostic threshold of the nomogram. RESULTS: This study included 924 patients, of whom 137 patients (14.8%) suffered from mild-CSPH and 66 patients suffered from (7.1%) with severe-CSPH confirmed preoperatively. Our data showed that preoperative prolonged prothrombin time, total bilirubin, indocyanine green retention rate at 15 min, CSPH grade, and standard future liver remnant volume were independent predictors of severe PHLF. By incorporating these factors, the nomogram achieved good prediction performance in assessing severe PHLF risk, and its concordance statistic was 0.891, 0.850 and 0.872 in the training cohort, internal validation cohort and external validation cohort, respectively, and good calibration curves were obtained. Moreover, the calculations of total points of diagnostic errors with 95% CI were concentrated in 110.5 (range 76.9-178.5). It showed a low risk of severe PHLF (2.3%), indicating hepatectomy is feasible when the points fall below 76.9, while the risk of severe PHLF is extremely high (93.8%) and hepatectomy should be rigorously restricted at scores over 178.5. Patients with points within the misdiagnosis threshold were further examined using CTREE according to a hierarchic order of factors represented by the presence of CSPH grade, ICG-R15, and sFLR. CONCLUSION: This new surgical scheme established in our study is practical to stratify risk classification in assessing severe PHLF, thereby facilitating surgical decision-making and identifying suitable candidates for individual hepatectomy.

Low bone turnover and reduced angiogenesis in streptozotocin-induced osteoporotic mice.

It is known that type 1 diabetes (T1D) reduces bone mass and increases the risk for fragility fractures, an effect that has been largely ascribed to decreased bone formation. However, the potential role of decreased angiogenesis as a factor in osteogenesis reduction has not been extensively studied. Furthermore, there is controversy surrounding the effect of T1D on bone resorption. This study characterized bone microstructure, bone strength, and bone turnover of streptozotocin (STZ)-induced diabetic mice (T1D mice) and explored the role of angiogenesis in the pathogenesis of T1D-induced osteoporosis. Results demonstrate that T1D deteriorated trabecular microarchitecture and led to reduced bone strength. Furthermore, T1D mice showed reduced osteoblast number/bone surface (N.Ob/BS), mineral apposition rate, mineral surface/BS, and bone formation rate/BS, suggesting attenuated bone formation. Decreased angiogenesis was shown by a reduced number of blood vessels in the femur and decreased expression of platelet endothelial cell adhesion molecule (CD31), nerve growth factor, hypoxia-inducible factor-1α, and vascular endothelial growth factor was observed. On the other hand, reduced bone resorption, an effect that could lead to impaired osteogenesis, was demonstrated by lower osteoclast number/BS and decreased tartrate-resistant acid phosphatase and cathepsin K mRNA levels. Reduced number of osteoblasts and decreased expression of receptor activator for nuclear factor-κB ligand could be responsible for compromised bone resorption in T1D mice. In conclusion, T1D mice display reduced bone formation and bone resorption, suggesting decreased bone turnover. Furthermore, this study points to impairments in angiogenesis as a pivotal cause of decreased bone formation.

Novel detoxifier of spironolactone against triptolide-induced hepatotoxicity through inhibition of RPB1 degradation.

ETHNOPHARMACOLOGICAL RELEVANCE: Triptolide is a major bioactive and toxic ingredient isolated from the traditional Chinese herb Tripterygium wilfordii (T. wilfordii) Hook F. It exhibits potent antitumor, immunosuppressive, and anti-inflammatory biological activities; however, its clinical application is hindered by severe systemic toxicity. Two preparations of T. wilfordii, including T. wilfordii glycoside tablets and T. wilfordii tablets, containing triptolide, are commonly used in clinical practice. However, their adverse side effects, particularly hepatotoxicity, limit their safe use. Therefore, it is crucial to discover potent and specific detoxification medicines for triptolide. AIM OF THE STUDY: This study aimed to investigate the detoxification effects and potential mechanism of action of spironolactone on triptolide-induced hepatotoxicity to provide a potential detoxifying strategy for triptolide, thereby promoting the safe applications of T. wilfordii preparations in clinical settings. MATERIALS AND METHODS: Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and crystal violet staining. Nuclear fragmentation was visualized using 4',6-diamidino-2-phenylindole (DAPI) staining, and protein expression was analyzed by Western blotting. The inhibitory effect of spironolactone on triptolide-induced hepatotoxicity was evaluated by examining the effects of spironolactone on serum alanine aminotransferase and aspartate aminotransferase levels, as well as liver pathology in a mouse model of triptolide-induced acute hepatotoxicity. Furthermore, a survival assay was performed to investigate the effects of spironolactone on the survival rate of mice exposed to a lethal dose of triptolide. The effect of spironolactone on triptolide-induced global transcriptional repression was assessed through 5-ethynyl uridine staining. RESULTS: Triptolide treatment decreased the cell viability, increased the nuclear fragmentation and the cleaved caspase-3 levels in both hepatoma cells and hepatocytes. It also increased the alanine aminotransferase and aspartate aminotransferase levels, induced the hepatocyte swelling and necrosis, and led to seven deaths out of 11 mice. The above effects could be mitigated by pretreatment with spironolactone. Additionally, molecular mechanism exploration unveiled that spironolactone inhibited triptolide-induced DNA-directed RNA polymerase II subunit RPB1 degradation, consequently increased the fluorescence intensity of 5-ethynyl uridine staining for nascent RNA. CONCLUSIONS: This study shows that spironolactone exhibits a potent detoxification role against triptolide hepatotoxicity, through inhibition of RPB1 degradation induced by triptolide and, in turn, retardation of global transcriptional inhibition in affected cells. These findings suggest a potential detoxification strategy for triptolide that may contribute to the safe use of T. wilfordii preparations.

Functions and action mechanisms of flavonoids genistein and icariin in regulating bone remodeling.

Increasingly natural products particularly flavonoids are being explored for their therapeutic potentials in reducing bone loss and maintaining bone health. This study has reviewed previous studies on the two better known flavonoids, genistein and icariin, their structures, functions, action mechanisms, relative potency, and potential application in regulating bone remodeling and preventing bone loss. Genistein, an isoflavone abundant in soy, has dual functions on bone cells, able to inhibit bone resorption activity of osteoclasts and stimulate osteogenic differentiation and maturation of bone marrow stromal progenitor cells (BMSCs) and osteoblasts. Genistein is an estrogen receptor (ER)-selective binding phytoestrogen, with a greater affinity to ERß. Genistein inhibits tyrosine kinases and inhibits DNA topoisomerases I and II, and may act as an antioxidant. Genistein enhances osteoblastic differentiation and maturation by activation of ER, p38MAPK-Runx2, and NO/cGMP pathways, and it inhibits osteoclast formation and bone resorption through inducing osteoclastogenic inhibitor osteoprotegerin (OPG) and blocking NF-κB signaling. Icariin, a prenylated flavonol glycoside isolated from Epimedium herb, stimulates osteogenic differentiation of BMSCs and inhibits bone resorption activity of osteoclasts. Icariin, whose metabolites include icariside I, icariside II, icaritin, and desmethylicaritin, has no estrogenic activity. However, icariin is more potent than genistein in promoting osteogenic differentiation and maturation of osteoblasts. The existence of a prenyl group on C-8 of icariin molecular structure has been suggested to be the reason why icariin is more potent than genistein in osteogenic activity. Thus, the prenylflavonoids may represent a class of flavonoids with a higher osteogenic activity.

[Effect of osthol on apoptosis and bone resorption of osteoclasts cultured in vitro].

This study is to investigate the effect of osthol on osteoclasts' activity, bone resorption as well as apoptosis in vitro, and explore the mechanism of osthol in preventing osteoporosis. Osteoclasts were separated from long-limb bones of new born rabbits, cultured in 24-well plate with glass slices and bone slices, and treated by 1 x 10(-5) mol x L(-1) osthol. Osteoclasts were identified by observing live cells with phase contrast microscope, HE staining, TRAP staining and toluidine blue staining of bone resorption pits. The numbers of bone resorption pits were counted as well as the surface area of bone resorption on bone slice. Osteoclasts were stained with acridine orange to detect the cell apoptosis. The ratio of apoptotic osteoclasts was observed under fluorescence microscope. The gene expression of RANKL, OPG, TRAP and p-JNK1/2 protein expression were examined using real time PCR and Western blotting, respectively. Comparing with the control group without osthol, the rates of apoptotic osteoclasts increased obviously and the number and area of bone resorption pits decreased evidently with 1 x 10(-5) mol x L(-1) osthol. There is significant difference between control group and experiment group treated by 1 x 10(-5) mol x L(-1) osthol. Therefore, the osthol through RANK+RANKL/TRAF6/Mkk/JNK signal pathway inhibits the osteoclasts activity, enhances osteoclasts apoptotic and inhibits the bone resorption.

[Photosynthetic characteristics of Drynaria fortunei and its relation to environmental factors].

OBJECTIVE: To have a better utilization of diurnal photosynthetic variation of Drynaria fortunei in three light environments and provide theoretical basis for its artificial cultivation. METHODS: Diurnal photosynthetic variation of Drynaria fortunei were determinated by portable photosynthesis analysis system (Li-6400), and correlation between physiological and environmental factors was further analysed. RESULTS: The diurnal net photosynthetic rate (NPR) exhibited a single peak curve, with the peak value of NPR occurring at 15:30. The mean diurnal Pn of D. fortunei in three environments followed a tread of tree epiphytes > shine > shade. WUE had significantly positive correlation with NPR. Air temperature (Ta), ambient CO2 concentration (Ca) and relative humidity (RH) were the main environmental factors for NPR of D. fortunei. CONCLUSION: The optimum cultivation condition of D. fortunei is 32 degrees C, RH around 40%, and appropriate shade is recommended.

Icariin is more potent than genistein in promoting osteoblast differentiation and mineralization in vitro.

There has been a strong interest in searching for natural therapies for osteoporosis. Genistein, an isoflavone abundant in soy, and icariin, a prenylated flavonol glycoside isolated from Epimedium Herb, have both been identified to exert beneficial effects in preventing postmenopausal bone loss. However, the relative potency in osteogenesis between the individual phytoestrogen flavonoids remains unknown. The present study compared ability of genistein and icariin in enhancing differentiation and mineralization of cultured rat calvarial osteoblasts in vitro. Dose-dependent studies in osteoblast differentiation measuring alkaline phosphatase (ALP) activity revealed optimal concentrations of genistein and icarrin for stimulating osteogenesis to be both at 10(-5) M. Time course studies comparing the two compounds both at 10(-5) M demonstrated that icariin treatment always produced higher ALP activity, more and larger areas of CFU-F(ALP) colonies and mineralized nodules, more osteocalcin secretion, and calcium deposition, and a higher level of mRNA expression of osteogenesis-related genes COL1α2, BMP-2, OSX, and RUNX-2. However, they inhibited the proliferation of osteoblasts to a similar degree. In conclusion, although future in vivo studies are required to investigate whether icariin is more efficient in improving bone mass and/or preventing bone loss, our in vitro studies have demonstrated that icariin has a stronger osteogenic activity than genistein. In addition, while the prenyl group on C-8 of icariin could be the active group that takes part in osteoblastic differentiation and explains its greater potency in osteogenesis, mechanisms of action, and reasons for the relative potency of icariin versus genistein need to be further studied.

Morphology of the cross section of silica layer in rice husk.

The physical adsorption of nitrogen and gas flow experiments on the silica layer in rice husk indicated that an existence of nano meter sized through holes. In this study, the external shape of the holes on the cross section of the layer was investigated with a scanning electron microscope equipped with an energy dispersive spectrometer, an atomic force microscope and scanning tunneling microscope. In the energy dispersive mapping image, 2-5 micron thick silica layer under outer cellulose layer, silica nano particles in the middle cellulose layer and sub micron silica layer in inner cellulose layer were observed. The cross section of the layer showed 20 nm building units with approximately 100 nm convexities. The atomic force microscopic image also showed the approximately 100 nm convexities as well as a roughness of approximately 20 nm. When osmium was coated on the silica layer, the wells with 2 approximately 5 nm horizontal and approximately 2 nm vertical lengths were observed on the plate surface in scanning tunneling microscopic image. From the results, it was suggested that the holes in the rice husk silica layer are almost straight and not zigzag spaces originated from the simple packing of nano particles.

Osthol, a coumarin isolated from common cnidium fruit, enhances the differentiation and maturation of osteoblasts in vitro.

The effect of osthol on osteoblasts was investigated in primary osteoblastic cells isolated from newborn Wistar rats. Osthol was supplemented into cultured medium at 10⁻7, 10⁻6, 10⁻5 and 10⁻4 mol/l, respectively. No stimulating effect was found on cell proliferation, but 10⁻5 mol/l osthol caused a significant increase in alkaline phosphatase (ALP) activity. Osteogenic differentiation markers were examined over a period of time at this concentration, and compared with control cells that were not supplemented with osthol. The results showed that the ALP activity, osteocalcin secretion and calcium deposition level in cells treated with osthol were 1.52, 2.74 and 2.0 times higher, respectively, than in the control cells. Results of ALP histochemical staining and mineralized bone nodule assays both showed that the number and area achieved in osthol-treated cells were 1.53-fold higher than in control cells. The gene expression of the growth and transcription factors basic fibroblast growth factor, insulin-like growth factor I, bone morphogenetic protein 2 (BMP-2), runt-related gene 2 (Runx-2) and osterix, which are associated with bone development, were also investigated. The increase in mRNA expression was 1.94, 1.74, 1.68, 1.83 and 2.31 times, respectively, higher compared to the control. Furthermore, osthol increased the protein expression of p38 mitogen-activated protein kinase (MAPK) and type I collagen. p38MAPK protein and collagen in osthol-treated cells were 1.42 and 1.58 times higher in osthol-treated cells compared to the control. The results of these studies support the conclusion that osthol significantly enhances the osteogenic differentiation of cultured osteoblasts. The results also indicated that osthol could stimulate the osteoblastic differentiation of rat calvarial osteoblast cultures by the BMP-2/p38MAPK/Runx-2/osterix pathway and that osthol may be used as an important compound in the development of new antiosteoporosis drugs.

[The changes of iNOS and NO in the osteogenic differentiation process of rat bone marrow stromal cells promoted by icariside II].

This study is to investigate the effects on the expression of iNOS and production of NO in the osteogenic differentiation process of rat bone marrow stromal cells (rBMSCs) by icariside II. rBMSCs were cultured by adherence screening method. When the culture dishes were covered with 80% cells, the osteogenic induced cultures were adopted. Icariside II was supplemented into the culture at 1 x 10(-5) mol x L(-1). The activity of iNOS, content of NO and osteogenic differentiation markers including alkaline phosphatase (ALP) activity, CFU-FALP and mineralized bone nodules were compared among the icariside II-supplemented group, L-NMAE group, icariside II + L-NAME group and the control. Total RNA was isolated and the gene expression of iNOS, Osterix and Runx-2 was investigated by real-time PCR. Total protein was also isolated and the secretion of iNOS and collagen I was examined by Western blotting. Icariside II can significantly improved ALP activity, CFU-FALP amount and mineralized nodules. Besides, the mRNA level of factors related to the osteogenic differentiation includes Osterix and Runx-2 also enhanced. The secretion of collagen I also promoted significantly. But all of these effects can be inhibited by L-NAME which can specifically inhibit the activity of iNOS. Icariside II enhances the osteogenic differentiation of rBMSCs significantly, but if the activity of iNOS was blocked by L-NAME, the osteogenic differentiation markers decrease accompanied with iNOS and NO decrease, suggesting that icariside II stimulates the osteogenic differentiation via enhancing the activity of iNOS and promoting the generation of NO.

[Effect of isopsoralen on the proliferation and differentiate of osteoblasts in vitro].

OBJECTIVE: To investigate the effect of isopsoralen on proliferation, osteogenic differentiation and calcification capacity of rat calvarial osteoblasts (ROB). METHODS: Segregated neonatal SD rat skull,and digestion with enzyme to obtain bone cells and cultured in MEM containing 10% FBS. Exchange the medium after three days, proceeded serial subcultivation when cells covered with 90% culture dish. Proliferation analysis was performed in 96-well plates use MTT method, isopsoralen's final concentration were 1 x 10(-4), 1 x10(-5), 1 x 10(-6), 1 x 10(-7) mmol/L. Differentiation analysis was performed in 24-well plates, the Alkaline phosphatase activity and calcium salt sediment yield and osteocalcin measured at the 4th, 8th, 12th, 16th day. At 12th day, proceeded ALP stain, and at 14th day for alizarin red staining and calcified nodule count. RESULTS: When the Isopsoralen's final concentration was 1 x 10(-5) mmol/L, there was no significant effect on the ROB's proliferation, but it could promote osteogenesis. It also could raise the ALP activity and calcium salt sediment yield and osteocalcin, increase calcified tubercle amount. CONCLUSION: When the isopsoralen final concentration is 1 x 10(-5) mmol/L, it promoted ROB differentiation and maturation. Isopsoralen may be the active ingredients of preventing anti-osteoporosis in Psoralea corylifolia.

[Comparative study on the osteogenic differentiation of rat bone marrow stromal cells effected by icariin and icariside II].

OBJECTIVE: To investigate the effects of icariin and it's main metabolites-icariside II on the osteogenic differentiation of rat bone marrow stromal cells (rBMSCs). METHODS: rBMSCs were cultured by adherence screening method, icariin and icariside II were supplemented into the culture at 5 x 10(-5) mol/L respectively. The osteogenic differentiation markers including alkaline phosphatase (ALP) activity, CFU-F(ALp), osteocalcin secretion, calcium deposition and mineralized bone modulus were compared among the icariin-supplemented group, icariside II and the control. The gene expressions of bFGF, IGF-1, Osterix and Runx-2 were examined by RT-Real Time PCR. RESULTS: Both icariside II and icariin significantly improved ALP activity, CFU-F(ALP) amount, osteocalcin secretion, calcium deposition and mineralized modulus. Besides, they enhanced the gene expressions of bFGF, IGF-1, Osterix and Runx-2. Icariside II was obviously stronger than icariin at the above activities. CONCLUSION: Icariside II is stronger than icariin at enhancing the osteogenic differentiation of rBMSCs, suggesting that icariin can be administered via oral and it's metabolites are the effective constitutes for antiosteoporosis activity.

Study of phosphodiesterase 5 inhibitors and α-adrenoceptor antagonists used alone or in combination for the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia.

INTRODUCTION: This study sought to compare the improvement in lower urinary tract symptoms (LUTS) and complications of phosphodiesterase type 5 inhibitors (PDE5i) and alpha-blockers (Abs) in combination or alone among males with benign prostatic hyperplasia (BPH). EVIDENCE ACQUISITION: We searched the PubMed, Embase, and Cochrane Library databases to identify all studied variables, including lower urinary tract symptoms (LUTS), BPH, Abs, and PDE5i and performed comparisons between combination treatment and single treatments as primary endpoints. Efficacy analysis including the International Prostate Symptom Score (IPSS), quality of life (QOL), maximum urinary flow rate (Qmax), postvoiding residual volume (PVR), and International Index of Erectile Function erectile function domain (IIEF-EF) score. Complications were also recorded. In addition, the secondary endpoint was a comparison of the efficacy and complications between the two single treatments. EVIDENCE SYNTHESIS: Nineteen studies involving 2,426 patients met the inclusion criteria. The data synthesized from these studies indicated that the combination treatment is better in efficiency than PDE5i or Abs alone in including IPSS (P<0.00001 in PDE5i; P=0.01 in Abs), QOL (P<0.00001 in PDE5i; P<0.00001 in Abs), Qmax (P<0.00001 in PDE5i; P<0.00001 in Abs), PVR (P=0.04 in PDE5i; P<0.00001 in Abs), and IIEF-EF (P<0.00001 in PDE5i; P<0.00001 in Abs). Regarding complications, only headache (P<0.00001), dyspepsia (P=0.01), and flushing (P=0.04) were more frequent in individuals undergoing the combination treatment. CONCLUSIONS: Combination treatment is more effective than PDE5i or Abs alone, though the side effects are not significantly different.

Changes of body immunity and inflammatory response in HIV/HCV co-infected patients.

Changes of body immunity and inflammatory response in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients were investigated. Eighty HIV/HCV infected patients admitted to Qingdao No. 6 People's Hospital from August 2015 to December 2017 were selected and divided into two groups according to whether they were complicated with HCV infection or not (n=40 per group). The changes of the related humoral immune indexes, the related cellular immune indexes, the related indexes of hepatic function, the related indexes of inflammatory response in the two groups were compared, and the correlations of high-sensitivity C-reactive protein (hs-CRP) level with alanine aminotransferase (ALT) level, immunoglobulin G (IgG) level and cluster of differentiation 4+ (CD4+) level in the observation group were analyzed. The levels of related humoral immune indexes [immunoglobulin G (IgG), IgA and IgM levels], the related cellular immune indexes (CD4+ and CD8+) in the observation group were lower than those in the control group (P<0.05), and the CD4+/CD8+ ratio in the observation group was lower than that in the control group (P<0.05). The levels of indexes of hepatic function [ALT, aspartate aminotransferase (AST) and total bilirubin] in the observation group were significantly higher than those in the control group (P<0.05). The levels of hs-CRP, interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) in the observation group were significantly higher than those in the control group (P<0.05). There were positive correlations of hs-CRP level with ALT level and IgG level in the observation group (P<0.05). There was a negative correlation between hs-CRP level and CD4+ level in the observation group (P<0.05). The humoral and cellular immune functions of the HIV/HCV co-infected patients are significantly limited, their hepatic function is significantly impaired and the levels of inflammatory cytokines are markedly increased. The level of hs-CRP is positively correlated with hepatic function and humoral immune function and negatively correlated with cellular immune function.

Is tamsulosin effective for the passage of symptomatic ureteral stones: A systematic review and meta-analysis.

BACKGROUND: Some trials have stated that there is no benefit to tamsulosin administration for clearing ureteral stones, which is contrary to previous studies. To confirm the efficacy of tamsulosin for treating symptomatic ureteral stones, we performed this review. METHODS: We searched the PubMed, Embase, and Cochrane Library databases to identify all studied variables, including tamsulosin, urinary stones, expulsion, and side effects. In addition, for all patients and different stone sizes, the treatment efficacy, expulsion rate, and expulsion time were also recorded for this treatment. RESULTS: Forty-nine studies involving 6436 patients met the inclusion criteria. The data synthesized from these studies indicated that tamsulosin improved the renal stone clearance rate (80.5% vs 70.5%; mean difference (MD), 1.16; 95% confidence interval (CI), 1.13-1.19; P <.00001) and reduced the expulsion time (MD, -3.61; 95% CI, -3.77 to -3.46; P ≤.00001). Regarding complications, no significant difference was found between the 2 groups in terms of the total side effects (MD, 1.15; 95% CI, 0.97-1.35; P = .10) or divided complications, including retrograde ejaculation (P = .01), hypotension (P = .52), dizziness (P = .07), diarrhea (P = .58), vomiting (P = .88), headache (P = .84), nausea (P = .91), and fatigue (P = .10). CONCLUSIONS: Tamsulosin should be strongly recommended for patients with ureteral stones to increase treatment efficacy. The side effects were not significantly different between the tamsulosin and control treatments.

Regulatory role of transforming growth factor beta subfamily in osteoarthritis / 中国组织工程研究

BACKGROUND:Osteoarthritis is one of the most common senile chronic degenerative diseases in China.Due to its complex pathogenesis and cellular molecular communication pathways,there is currently no effective method to slow down the progression of osteoarthritis.Studies have found that transforming growth factor-β is one of the key factors in the maintenance and regulation of joint stability and plays a significant role in the formation of early joints,as well as the development of bone and cartilage,and the remodeling of joints at various stages. OBJECTIVE:To review the regulatory role of the transforming growth factor-β subfamily in the occurrence and development of osteoarthritis,both domestically and internationally in recent years,to analyze the impacts it has at different stages of osteoarthritis,and to explore the potential application prospects of transforming growth factor-β in the clinical treatment of osteoarthritis,with a view to informing clinical treatment protocols.. METHODS:The relevant articles were searched by computer from CNKI Database and PubMed Database.The search terms were"osteoarthritis,transforming growth factor,signaling pathway,bone remodeling,cartilage degeneration,angiogenesis,treatment"in Chinese and English,respectively.Finally,57 articles were included for review. RESULTS AND CONCLUSION:The pathogenesis of osteoarthritis remains a subject of ongoing exploration with no unified consensus.Numerous studies highlight the close correlation between osteoarthritis and cytokines,focusing on the transforming growth factor-β superfamily as a pivotal mechanism and therapeutic breakthrough.Transforming growth factor-β plays a crucial role in early joint cartilage formation and maintenance,promoting cartilage repair.However,post-joint formation,its protective effect weakens,leading to potential destructive consequences.This dual regulatory role is a current clinical treatment focus,necessitating further research to delineate its application scope for standardized protocols.Highly active transforming growth factor-β participates in the regulation of bone cells,osteoblasts,and osteoclasts under mechanical stress,and intervenes in the subsequent remodeling of bone microstructure.Specific inhibitors present potential targeted therapeutics,yet their safety and efficacy in clinical settings require refinement.Vascular proliferation may serve as a potential disruptive pathway in transforming growth factor-β-mediated cartilage degeneration and subchondral bone remodeling.Abnormal communication pathways can further disrupt the homeostasis of the microenvironment of osteochondral units,thereby accelerating key pathological progressions of osteoarthritis.Research on transforming growth factor-β in osteoarthritic contexts is comprehensive,holding broad clinical application prospects.Drugs related to transforming growth factor-β are in clinical trial phases,but addressing potential impacts on other tissues and precise control of targeted delivery are critical concerns.As research advances,there is optimism for innovative breakthroughs in slowing the progression of osteoarthritis in the future.

CD3+, CD4+, and CD8+ Expression in Cells in Peripheral Blood of Silicosis Patients and Intervention Effect of Thymalfasin.

OBJECTIVE: This study aims to investigate the changes in CD3+, CD4+ and CD8+ expression in cells in peripheral blood of silicosis patients, and observe the immunoregulatory effect of thymalfasin. METHODS: A total of 80 silicosis patients were enrolled in the study, randomly divided into two groups: treatment group and control group (n=40, each group). In addition, 40 healthy adults, who underwent physical examinations in our hospital, were enrolled into the health examination group. Patients in the control group and treatment group were given anti-infection treatment, according to their conditions. Patients in the treatment group additionally received thymalfasin. Then, the number of peripheral blood T lymphocyte subsets in subjects in all three groups before and after treatment was measured. RESULTS: (1) Before treatment, CD3+, CD4+ and CD8+ levels in cells were significantly lower in the treatment group and control group than in the health examination group, and the differences were statistically significant (P<0.05). (2) In the treatment group, the number of CD4+ cells in peripheral blood was significantly higher after one week of treatment, when compared to that before treatment, and the difference was statistically significant (P<0.05). CONCLUSION: In silicosis patients, CD3+, CD4+ and CD8+ cells in peripheral blood are decreased, and thymalfasin can significantly increase CD4+ cells in peripheral blood of silicosis patients.

Isolation distance between municipal solid waste landfills and drinking water wells for bacteria attenuation and safe drinking.

Groundwater pollution and human health risks caused by leachate leakage have become a worldwide environmental problem, and the harm and influence of bacteria in leachate have received increased attention. Setting the isolation distance between landfill sites and groundwater isolation targets is particularly important. Firstly, the intensity model of pollutant leakage source and solute transport model were established for the isolation of pathogenic Escherichia coli. Then, the migration, removal and reduction of bacteria in the aerated zone and ground were simulated. Finally, the isolation distance was calculated based on the acceptable water quality limits, and the influence of hydrogeological arameters was analyzed based on the parameter uncertainty. The results of this study suggest that the isolation distances vary widely ranging from 106 m-5.46 km in sand aquifers, 292 m-13.5 km in gravel aquifers and 2.4-58.7 km in coarse gravel aquifers. The gradient change of groundwater from 0.001 to 0.05 resulted in the isolation distance at the highest gradient position being 2-30 times greater than that at the lowest gradient position. There was a difference in the influence of the thickness of the vadose zone. For example, under the same conditions, with the increase of the thickness of the aeration zone, the isolation distance will be reduced by 1.5-5 times, or under the same thickness of the aeration zone, the isolation distance will be significantly shortened. Accordingly, this needs to be determined based on specific safety isolation requirements. In conclusion, this research has important guiding significance for the environmental safety assessment technology of municipal solid waste landfill.