Natural products in traditional Chinese medicine: molecular mechanisms and therapeutic targets of renal fibrosis and state-of-the-art drug delivery systems.

Renal fibrosis (RF) is the end stage of several chronic kidney diseases. Its series of changes include excessive accumulation of extracellular matrix, epithelial-mesenchymal transition (EMT) of renal tubular cells, fibroblast activation, immune cell infiltration, and renal cell apoptosis. RF can eventually lead to renal dysfunction or even renal failure. A large body of evidence suggests that natural products in traditional Chinese medicine (TCM) have great potential for treating RF. In this article, we first describe the recent advances in RF treatment by several natural products and clarify their mechanisms of action. They can ameliorate the RF disease phenotype, which includes apoptosis, endoplasmic reticulum stress, and EMT, by affecting relevant signaling pathways and molecular targets, thereby delaying or reversing fibrosis. We also present the roles of nanodrug delivery systems, which have been explored to address the drawback of low oral bioavailability of natural products. This may provide new ideas for using natural products for RF treatment. Finally, we provide new insights into the clinical prospects of herbal natural products.

Preliminary study of short-term outcomes and learning curves of robotic-assisted THA: comparison between closed platform robotic system and open platform robotic system.

BACKGROUND: Both closed platform and open platform robotic-assisted total hip arthroplasty (THA) have recently been recommended as a viable treatment option for achieving accurate positioning of components. Yet, limited studies paid attention to the differences between the closed platform robotic system and the open platform robotic system. Hence, this study aimed to investigate clinical outcomes, radiographic outcomes, complication rates and learning curve of two systems. MATERIALS AND METHODS: We retrospectively included 62 patients (31 closed robotic system and 31 open robotic system) who underwent THA between February 2021 and January 2023. The demographics, operating time, cup positioning, complications and hip Harris score were evaluated. Learning curves of operation time was conducted using cumulative sum (CUSUM) analysis. RESULTS: There were no differences in surgical time (76.7 ± 12.1 min vs. 72.3 ± 14.8 min), estimated blood loss (223.2 ± 13.2 ml vs. 216.9 ± 17 ml) and Harris Hip score (HHS) between closed platform robotic system and the open platform robotic system. The closed robotic system and the open robotic system were associated with a learning curve of 9 cases and 7 cases for surgical time respectively, based on the satisfying rate of Lewinnek's safe zone outliers (1/31, 96.8%) and no occurrence of complication. Both robotic systems had significant reduction in overall surgical time, the duration of acetabulum registration, and estimated blood loss between learning phase and proficiency phase. CONCLUSION: The authors suggest that the surgical outcomes and safe zone outlier rate of the open robotic-assisted THA were similar to those of the closed robotic-assisted THA. These two robotic-assisted are associated with comparable learning curves and both have the precise positioning of acetabular component. From learning phase to proficiency phase, the rate of positions within the safe zone differed only marginally (88.9-100% vs. 85.7-100%) based on a rather low number of patients. This is not a statistically significant difference. Therefore, we suggest that THA undergoing with the robotic-assisted system is the relatively useful way to achieve planned acetabular cup position so far.

Outcomes of dual mobility articulation total hip arthroplasty in ipsilateral residual poliomyelitis.

BACKGROUND: Patients with poliomyelitis underwent total hip arthroplasty (THA) are known to be at higher risk of dislocation on account of muscular atrophy. This study aimed to investigate clinical outcomes, radiographic outcomes, complication rates, and survivorship of dual mobility THA in displaced femoral neck fractures of elderly with poliomyelitis. MATERIALS AND METHODS: We retrospectively included 17 patients (17 hips) with residual poliomyelitis who underwent THA with dual mobility articulation. Clinical outcomes were assessed with the visual analog scale (VAS) pain score, Oxford hip score, and University of California Los Angeles activity (UCLA) score. Radiographic outcomes were examined by radiographs. Complications and re-operations following THA were recorded. RESULTS: The mean follow-up period was 77.05 months. The mean VAS, Oxford hip score, and UCLA score were improved significantly. In all but one patient, no complications were occurred. Re-operation was carried out in one patient due to posterior dislocation. The Kaplan-Meier survivorship with an end point of re-operation for any reason was 94.1%. CONCLUSIONS: THA with dual mobility system is proved to be effective in strengthening stability and reducing the risk of dislocation, which is suitable for patients with neuromuscular disease. Hence, in elderly with residual poliomyelitis, dual mobility THA is a valid choice as a treatment for displaced femoral neck fractures.

The role of routine postoperative laboratory tests following hip hemiarthroplasty for an elderly femoral neck fracture.

BACKGROUND: Performing postoperative laboratory tests following joint arthroplasty is a regular practice. However, the role of routine postoperative laboratory tests in primary hip arthroplasty is currently in doubt. This study aimed to assess the role of routine postoperative laboratory tests for femoral neck fractures in elderly patients who underwent hip hemiarthroplasty and to evaluate the risk factors for postoperative laboratory testing abnormalities and related interventions. METHODS: This retrospective study reviewed 735 consecutive patients with femoral neck fractures (FNFs) who underwent hip hemiarthroplasty at a single tertiary academic organization. Patient characteristic features and laboratory testing values were recorded. Logistic regression models were calculated to identify risk factors. RESULTS: A total of 321 elderly patients (> 75 years of age) were ultimately enrolled for analysis. Abnormal postoperative laboratory tests were found in 265 patients (82.6%). Only a minority of the included patients (7.5%) needed medical intervention to treat postoperative laboratory testing abnormalities. Multivariate logistic regression analysis reported that a higher Charlson comorbidity index (CCI) (P = 0.03), abnormal preoperative haemoglobin level (P < 0.01), higher intraoperative blood loss (P < 0.01) and less frequent tranexamic acid use (P = 0.05) were risk factors for abnormal postoperative laboratory tests. Furthermore, a higher CCI has been identified as a risk factor for patients needing clinical interventions related to laboratory abnormalities. CONCLUSIONS: Because 92.5% of laboratory tests did not influence postoperative management, the authors suggest that routine laboratory tests after hip hemiarthroplasty for FNFs are less instructive for the majority of elderly patients. Nevertheless, for patients with identified risk factors, postoperative laboratory tests are still required to identify the abnormalities that need to be managed.

Diabetes mellitus accelerates the progression of osteoarthritis in streptozotocin-induced diabetic mice by deteriorating bone microarchitecture, bone mineral composition, and bone strength of subchondral bone.

BACKGROUND: The purpose of this study was to develop an optimal diabetes-osteoarthritis (DM-OA) mouse model to validate that diabetes aggravates osteoarthritis (OA) and to evaluate the microarchitecture, chemical composition, and biomechanical properties of subchondral bone (SB) as a consequence of the DM-OA-induced damage induced. METHODS: Mice were randomly divided into three groups: DM-OA group, OA group, and sham group. Blood glucose levels, body weight, and food intake of all animals were recorded. Serum calcium (Ca) and osteocalcin (OCN) levels were compared in the three groups. The messenger ribonucleic acid (mRNA) and protein expression of key regulators for bone metabolism were detected. A semi-quantitative grading system [Osteoarthritis Research Society International (OARSI)] was used to evaluate cartilage and SB degeneration. Microspectroscopy, microindentations, micro-computed tomography (CT) imaging, and fracture load of compression testing were also used to evaluate trabecular SB properties. RESULTS: Glycemic monitoring and pancreas pathological results indicated stable high blood glucose and massive destruction of pancreas and islet cells in the DM-OA group. Serum levels of bone specific alkaline phosphatase (ALP-B) and tartrate-resistant acid phosphatase 5b (TRACP-5b) in the DM-group were higher than those of the other two groups while levels of serum Ca and OCN were lower. Meanwhile, the protein and mRNA expression of osteoblast-specific biomarkers [osteoprotegerin/receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) ratio, collagen type I (COL-I), Runt-related transcription factor 2 (RUNX-2), OCN] were suppressed, and osteoclast-specific biomarkers [sclerostin (SOST)] was elevated in the DM-OA group. The mineral-to-collagen ratio, microindentation elastic modulus, hardness, micro-architectural parameters, bone mineral density, and fracture load of SB trabecular bone of the DM-OA group joint were lower than those of the other two groups. On the other hand, The OARSI score, trabecular spacing, and structural model index of the DM-OA group joint were higher than those of the other two groups. CONCLUSIONS: The glycemic and pancreatic pathological results indicated that the DM-OA model was a simple and reliable model induced by streptozotocin (STZ) and surgery. The results revealed the mechanisms through which diabetes accelerates OA; that is, by damaging and deteriorating the functions of SB, including its microarchitecture, chemical composition, and biomechanical properties.

[Herbalogical study on original plant and medicinal and edible values of Citri Sarcodactylis Fructus].

Citri Sarcodactylis Fructus is a both medicinal and edible species specified by the China Ministry of Health, with a long history in China. According to the ancient monographs about materia medica, it was found that the records of the Citri Sarcodactylis Fructus on the original plants were confused. This paper reviewed the ancient monographs about materia medica, and made a summarization and textual research on the name, origin, habitat, processing methods, medicinal properties and clinicacy efficacy of Citri Sarcodactylis Fructus based the comprehensive analysis on modern literatures and authoritative books of Chinese herbal medicine. The results indicated that there were many bynames of Citri Sarcodactylis Fructus. Before the Yuan Dynasty, there was a mixed use of Citri Sarcodactylis Fructus and Citri Fructus, which were not distinguished from each other in terms of nature and taste until the Yuan dynasty. Citri Sarcodactylis Fructus was a varietas of Citri Fructus. The main shape of the original plant of Citri Sarcodactylis Fructus is "like a human hand with fingers" as recorded in ancient monographs about materia medica. The main places of origin of Citri Sarcodactylis Fructus were Guangdong, Zhejiang, Fujian, Sichuan, which were relatively stable. There were fewer records about medicinal proces-sing methods of Citri Sarcodactylis Fructus. Only steaming and baking methods were found in ancient monographs about materia medica, and the steaming method could reduce the irritability of Citri Sarcodactylis Fructus. The processing of therapeutic dietary of Citri Sarcodactylis Fructus was widely used in folk, which was represented by Chaozhou Laoxianghuang, a traditional succade made of Citri Sarcodactylis Fructus. According to the 2015 edition of Chinese Pharmacopoeia, Citri Sarcodactylis Fructus had effects in soothing liver and regulating gas, relieving pain in the stomach, eliminating dampness and resolving phlegm, which was basically consistent with the descriptions in ancient monographs about materia medica. This paper defined the original plant of Citri Sarcodactylis Fructus, and sorted out and summarized the processing methods, nature and taste of Citri Sarcodactylis Fructus, so as to provide data support for the standardization of the processing technology and the development and utilization of Citri Sarcodactylis Fructus.

Transgelin interacts with PARP1 in human colon cancer cells.

BACKGROUND: Transgelin, an actin-binding protein, is associated with cytoskeleton remodeling. Findings from our previous studies demonstrated that transgelin was up-regulated in node-positive colorectal cancer (CRC) versus node-negative disease. Over-expression of TAGLN affected the expression of 256 downstream transcripts and increased the metastatic potential of colon cancer cells in vitro and in vivo. This study aims to explore the mechanisms through which transgelin participates in the metastasis of colon cancer cells. METHODS: Immunofluorescence and immunoblotting analysis were used to determine the cellular localization of endogenous and exogenous transgelin in colon cancer cells. Co-immunoprecipitation and subsequently high-performance liquid chromatography/tandem mass spectrometry were performed to identify the proteins that were potentially interacting with transgelin. The 256 downstream transcripts regulated by transgelin were analyzed with bioinformatics methods to discriminate the specific key genes and signaling pathways. The Gene-Cloud of Biotechnology Information (GCBI) tools were used to predict the potential transcription factors (TFs) for the key genes. The predicted TFs corresponded to the proteins identified to interact with transgelin. The interaction between transgelin and the TFs was verified by co-immunoprecipitation and immunofluorescence. RESULTS: Transgelin was found to localize in both the cytoplasm and nucleus of the colon cancer cells. Approximately 297 proteins were identified to interact with transgelin. The overexpression of TAGLN led to the differential expression of 184 downstream genes. Network topology analysis discriminated seven key genes, including CALM1, MYO1F, NCKIPSD, PLK4, RAC1, WAS and WIPF1, which are mostly involved in the Rho signaling pathway. Poly (ADP-ribose) polymerase-1 (PARP1) was predicted as the unique TF for the key genes and concurrently corresponded to the DNA-binding proteins potentially interacting with transgelin. The interaction between PARP1 and transgelin in human RKO colon cancer cells was further validated by immunoprecipitation and immunofluorescence assays. CONCLUSIONS: Our results suggest that transgelin binds to PARP1 and regulates the expression of downstream key genes, which are mainly involved in the Rho signaling pathway, and thus participates in the metastasis of colon cancer.

[Historical evolution of Coicis Semen processing methods].

Coicis Semen is widely used as a raw material which can be used as both medicine and food among people. According to the ancient monographs on materia medica and relevant documents on the processing specifications in various provinces and cities, herba logical study on the historical evolution of the processing methods of Coicis Semen was conducted in this paper from the aspects of collecting and processing methods of Coicis Semen, the processing methods in the past dynasties and the nature, flavour and efficacy of Coicis Semen. The results showed that the processing methods of Coicis Semen recorded in monographs on materia medica mainly included stir-frying, glutinous rice stir-frying, salt processing(including salt cooking and salt stir-frying), stir-frying with the earth scraped from the wall facing east, and ginger juice stir-frying, etc. Among them, stir-frying, and stir-frying with the earth scraped from the wall facing east are still used nowadays. The bran stir-frying is the improved version of glutinous rice stir-frying in order to be adaptive to the modern-day situation and the needs of the present. In addition, the ancient shell removal and kernel keeping method are also included in the processing procedures in modern local processing specifications, which are combined with frying to form a new method named "Fazhi" processing( "Fazhi" means a processing method of multiple procedures). The 2015 edition of Chinese Pharmacopoeia records that Coicis Semen is helpful to clear dampness and promote diuresis, strengthen the spleen and prevent diarrhea, eliminate impediment, discharge pus, resolve toxin and a mass, etc., which are consistent with those contained in ancient monographs on materia medica. After the "Fazhi" processing, the cold nature of Coicis Semen has been removed and its nature,flavour and meridian tropism have been changed, so its application scopes expanded. The results of this study clearly traced the history of the collecting and proces-sing of Coicis Semen, summarized the nature, flavour and efficacy of Coicis Semen contained in both ancient and modern literature, and provided a historical basis for the standardization of the subsequent processing technology of Coicis Semen, the clinical application of various processed products, and the further development and utilization of medicinal materials.

Hemiarthroplasty compared with internal fixation for treatment of nondisplaced femoral neck fractures in elderly patients: a retrospective study.

INTRODUCTION: Internal fixation (IF) with cannulated screws is the most widely accepted operation method for nondisplaced femoral neck fractures (FNFs) in elderly patients. However, there were higher rate of reoperation, severe complications and poorer functional outcomes reported in these patients treated with IF. The purpose of this research is to compare the prognosis, complications, reoperation and mortality of bipolar hemiarthroplasty (HA) with IF of cannulated screws in elderly patients. METHODS: All elderly patients (>75 years of age) with nondisplaced FNFs from January 2010 to December 2015 at our institution were included in this study. Patients treated with HA and IF with cannulated screws were compared. Outcome measures included the surgical complications, perioperative parameters, hip joint function, reoperation and mortality. RESULTS: The blood loss of HA group (150.0 ± 55.1 mL) was statistically more than IF group (40.5 ± 15.7 mL, p = 0.001). However, the blood transfusion rate was similar between two groups (p = 0.102). At the last follow-up, there were total 14 (34.1%) severe surgical complications in the IF group, compared to 9 (10.1%) in the HA group (P = 0.001). No difference was detected between two groups with respect to the HHS and VAS at the last follow-up. Compared with the HA group, the IF group had much more reoperation in the follow up period (p = 0.001). There was no statistically differences of mortality rate between HA group (39.3%, 35/89) and IF group (34.1%, 14/41) (p=0.571). CONCLUSIONS: As a treatment option for nondisplaced intracapsular FNFs in elderly patients, HA showed the merits of a less surgical complications and less reoperations, while IF demonstrated a shorter surgical time and less intraoperative blood loss. Meanwhile, there was no significant difference in the hip joint function and mortality rate in midterm follow-up. Further evaluation with a longer follow-up is recommended to strengthen these findings.

Atomic Force Microscopy-Based Nanoscopy of Chondrogenically Differentiating Human Adipose-Derived Stem Cells: Nanostructure and Integrin ß1 Expression.

Integrin ß1 is known to be involved in differentiation, migration, proliferation, wound repair, tissue development, and organogenesis. In order to analyze the binding probability between integrin ß1 ligand and cluster of differentiation 29 (CD29) receptors, atomic force microscopy (AFM) was used to detect native integrin ß1-coupled receptors on the surface of human adipose-derived stem cells (hADSc). The binding probability of integrin ß1 ligand-receptor interaction was probed by integrin ß1-functionalized tips on hADSc during early chondrogenic differentiation at the two-dimensional cell culture level. Cell morphology and ultrastructure of hADSc were measured by AFM, which demonstrated that long spindled cells became polygonal cells with decreased length/width ratios and increased roughness during chondrogenic induction. The binding of integrin ß1 ligand and CD29 receptors was detected by ß1-functionalized tips for living hADSc. A total of 1200 curves were recorded at 0, 6, and 12 days of chondrogenic induction. Average rupture forces were, respectively, 61.8 ± 22.2 pN, 60 ± 20.2 pN, and 67.2 ± 22.0 pN. Rupture events were 19.58 ± 1.74%, 28.03 ± 2.05%, and 33.4 ± 1.89%, respectively, which demonstrated that binding probability was increased between integrin ß1 ligand and receptors on the surface of hADSc during chondrogenic induction. Integrin ß1 and the ß-catenin/SOX signaling pathway were correlated during chondrogenic differentiation. The results of this investigation imply that AFM offers kinetic and visual insight into the changes in integrin ß1 ligand-CD29 receptor binding on hADSc during chondrogenesis. Changes in cellular morphology, membrane ultrastructure, and the probability of ligand-transmembrane receptor binding were demonstrated to be useful markers for evaluation of the chondrogenic differentiation process.

[The relationship between PMI and concentration of potassium ion and sodium ion in swine aqueous humor after death].

OBJECTIVE: To explored the relationship between the concentration of potassium ion as well as sodium ion in the aqueous humor and post-mortem interval (PMI). METHODS: The concentrations of potassium ion and sodium ion in the aqueous humor of swine within 48 h after death at 4 degrees C and 28 degrees C were detected using Z-500 atomic absorption spectrophotometer. RESULTS: The concentrations of potassium ion and sodium ion in aqueous humor of isolated swine eyeballs within 48 h after death when the environmental temperature was 4 degrees C were significantly related to PMI. The relationship between PMI and the concentration of potassium ion was PMI = -0.178[K+]2 + 49.978 (R2 = 0.995). The relationship between PMI and the rate of sodium ion and potassium ion was PMI = 120.987/[Na+/K+]-28.834 (R2 = 0.905). CONCLUSION: The concentration of potassium in aqueous humor of isolated swine eyeballs may be one of the reference indicators to estimate PMI of the corpses at lower temperatures.

[Survivin and COX-2 expressions in giant cell tumor of bone and their relation to the prognosis].

OBJECTIVE: To investigate the expression of survivin and COX-2 in giant cell tumor of bone (GCT) and explore the prognostic factors for GCT. METHODS: The expressions of survivin and COX-2 in 39 GCT tissues of three Jaffe grades and 4 normal bone tissues were detected by immunohistochemical staining, and the data were analyzed in relation to the clinicopathological features of the patients. RESULTS: The expressions of survivin and COX-2 were significantly higher in the GCT tissues than in normal bone tissues (P<0.01). A positive correlation was found between survivin and COX-2 expressions and the pathological grade (P<0.01), but their expressions were not correlated to the patients' gender, age or surgical approaches (P>0.05). An obviously lowered recurrence rate was observed in patients with resection of the bone segment compromised by the tumor and subsequent bone grafting. Survivin and COX-2 were not independent risk factors of the prognosis of GCT. CONCLUSION: Survivin and COX-2 expressions may participate in the pathogenesis and development of GCT, but is not indicative of the prognosis.

[Immunohistochemical study of fibronectin in multiple organ dysfunction syndrome in elderly rats].

OBJECTIVE: To study the characteristic of endothelial injuries and the mechanisms of coagulation disorder in multiple organ dysfunction syndrome in elderly rats by observing the distribution and the intensity of fibronectin (FN) expression in important viscerae including the heart, brain, lung, kidney, liver. METHODS: Fifty Wistar rats (one half of them were 3 months old, another half 20 months old) were anaesthetized and cecal ligation puncture (CLP) was done. They were defined as MODS group and MODSE group. Forty Wistar rats (one half of them 3 months old, another half 20 months old) were anaesthetized and laparotomy was done as sham operation group (SOG) and sham operation group in elderly (SOGE). The heart, brain, lung, liver and kidney were harvested and were examined histologically at 6, 12, 24, 48 or 72 hours after operation. They were also stained immunohistochemically by using anti-FN as the first antibody. RESULTS: The expression of FN on the surfaces of vascular endothelial cells in hearts, brains, lungs, livers, kidneys was weakly positive or positive in MODSE, MODS or SOGE group, but it was positive or strongly positive in SOG group. The differences were significant (P<0.05). CONCLUSION: The injury of endothelial cells and the disorders of coagulation system are observed in MODSE, MODS, SOGE groups, especially in MODSE.

[Immunohistochemical study of thrombomodulin expression in multiple organs dysfunction syndrome].

OBJECTIVE: To study the expression of thrombomodulin (TM) and its significance in the pathogenesis of multiple organs dysfunction syndrome (MODS). METHODS: TM expression was determined by immunohistochemical staining in 20 autopsy cases with MODS group and 12 autopsy cases without MODS (control group). RESULTS: Significant differences in positive expression of TM in heart, lungs and kidneys were found between the control group and MODS group (all P<0.01). CONCLUSION: The increase of TM secretion results in homeostatic disturbance, which might be one of the important mechanisms of MODS.