Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

BACKGROUND:Due to the sudden release and the rapid removal by proteases,platelet-rich plasma hydrogel leads to shorter residence times of growth factors at the wound site.In recent years,researchers have focused on the use of hydrogels to encapsulate platelet-rich plasma in order to improve the deficiency of platelet-rich plasma hydrogels. OBJECTIVE:To prepare self-assembled polypeptide-platelet-rich plasma hydrogel and to explore its effects on the release of bioactive factors of platelet-rich plasma. METHODS:The self-assembled polypeptide was synthesized by the solid-phase synthesis method,and the solution was prepared by D-PBS.Hydrogels were prepared by mixing different volumes of polypeptide solutions with platelet-rich plasma and calcium chloride/thrombin solutions,so that the final mass fraction of polypeptides in the system was 0.1%,0.3%,and 0.5%,respectively.The hydrogel state was observed,and the release of growth factors in platelet-rich plasma was detected in vitro.The polypeptide self-assembly was stimulated by mixing 1%polypeptide solution with 1%human serum albumin solution,so that the final mass fraction of the polypeptide was 0.1%,0.3%,and 0.5%,respectively.The flow state of the liquid was observed,and the rheological mechanical properties of the self-assembled polypeptide were tested.The microstructure of polypeptide(mass fraction of 0.1%and 0.001%)-human serum albumin solution was observed by scanning electron microscope and transmission electron microscope. RESULTS AND CONCLUSION:(1)Hydrogels could be formed between different volumes of polypeptide solution and platelet-rich plasma.Compared with platelet-rich plasma hydrogels,0.1%and 0.3%polypeptide-platelet-rich plasma hydrogels could alleviate the sudden release of epidermal growth factor and vascular endothelial growth factor,and extend the release time to 48 hours.(2)After the addition of human serum albumin,the 0.1%polypeptide group still exhibited a flowing liquid,the 0.3%polypeptide group was semi-liquid,and the 0.5%polypeptide group stimulated self-assembly to form hydrogel.It was determined that human serum albumin in platelet-rich plasma could stimulate the self-assembly of polypeptides.With the increase of the mass fraction of the polypeptide,the higher the storage modulus of the self-assembled polypeptide,the easier it was to form glue.(3)Transmission electron microscopy exhibited that the polypeptide nanofibers were short and disordered before the addition of human serum albumin.After the addition of human serum albumin,the polypeptide nanofibers became significantly longer and cross-linked into bundles,forming a dense fiber network structure.Under a scanning electron microscope,the polypeptides displayed a disordered lamellar structure before adding human serum albumin.After the addition of human serum albumin,the polypeptides self-assembled into cross-linked and densely arranged porous structures.(4)In conclusion,the novel polypeptide can self-assemble triggered by platelet-rich plasma and the self-assembly effect can be accurately adjusted according to the ratio of human serum albumin to polypeptide.This polypeptide has a sustained release effect on the growth factors of platelet-rich plasma,which can be used as a new biomaterial for tissue repair.

Peptide-based hydrogel, the polymer materials with a special network structure, are widely used in various fields of biomedicine due to their stable properties and biocompatibility. Environment-responsive self-assembled peptide aqueous solutions can respond to environment changes by the self-assembly of peptides into nanofiber networks. Peptide-based hydrogels well simulate the extracellular matrix and cell growth microenvironment, being suitable for 3D cell culture and organoid culture. To establish a tumor organoid culture system with peptide-based hydrogels, we cultured Panc-1, U87, and H358 cells in a 3D spherical manner using CulX Ⅱ peptide-based hydrogels in 24-well plates for 15 days. The organoids showed a 3D spherical shape, and their sizes increased with the extension of the culture time, with a final diameter ranging from 150 to 300 μm. The organoids had a large number, varying sizes, good cell viability, clear edges, and a good shape, which indicated successful organoid construction. The tumor organoid culture system established in this study with CulX Ⅱ peptide-based hydrogels provides a model for studying tumor pathogenesis, drug development, and tumor suppression.
Hydrogels/chemistry* ; Organoids ; Humans ; Peptides/pharmacology* ; Cell Line, Tumor ; Cell Culture Techniques, Three Dimensional ; Cell Culture Techniques ; Cell Survival/drug effects* ; Nanofibers/chemistry*

Objective:To investigate the characteristics of fragility fractures of pelvis(FFP) in the elderly and compare the clinical efficacy between conservative treatment and minimally invasive surgery.Methods:A retrospective study was conducted in the 56 elderly FFP patients who had been treated at Department of Orthopaedics, The General Hospital of Chinese People＇s Liberation Army from January 2017 to January 2019. They were 16 males and 40 females, with an age of 73.4 years (from 65 to 93 years). By the American Society of Anesthesiologists (ASA) classification, there were 12 cases of grade Ⅰ, 16 cases of grade Ⅱ, 20 cases of grade Ⅲ, and 8 cases of grade Ⅳ; by the FFP classification, there were 6 cases of type Ⅰ, 10 cases of type Ⅱ, 36 cases of type Ⅲ, and 4 cases of type Ⅳ. The morphological characteristics and injury mechanisms of FFP were analyzed. According to the treatment methods, the patients were divided into a conservative treatment group of 32 cases and a minimally invasive surgery group of 24 cases. The 2 groups were compared in terms of complication incidence, mortality and the Koval attenuation rate of walking ability after one-year follow-up.Results:There were mostly the fractures of pubic branches on both sides of the pubic symphysis and compression fractures of the sacral wing caused by lateral crush injury. The 2 groups were comparable due to no significant differences in the preoperative general data between them other than FFP classification ( P>0.05). By one year after treatment, the conservative treatment group had a complication incidence of 34.4% (11/32), a mortality of 9.4% (3/32) and a Koval attenuation rate of walking ability of 13.8% (4/29) while the minimally invasive surgery group had a complication incidence of 20.8% (5/24), a mortality of 4.2% (1/24) and a Koval attenuation rate of walking ability of 8.7%(2/23), showing no significant difference between the 2 groups ( P>0.05). Conclusions:The injury mechanism of geriatric FFP is mostly lateral compression injury. The fracture sites are mostly located on both sides of the pubic symphysis, pubic branches and the sacral wing of anterior and posterior rings simultaneously. Although there may be no significant difference in complication incidence, mortality or Koval attenuation rate of walking ability between conservative treatment and minimally invasive surgery after one year, the minimally invasive surgery deals with more unstable fracture types.

Objective:To analyze the clinical-pathological data of patients with locally advanced rectal cancer who underwent modified total neoadjuvant therapy (TNT), and to evaluate the safety and efficacy of radical surgery after modified total neoadjuvant therapy.Methods:The clinical-pathological data of 30 locally advanced rectal cancer patients who underwent modified TNT (mTNT) followed by radical resection were retrospectively analyzed. The surgical procedure, postoperative complications, tumor regression grade, tumor downstaging and prognosis were analyzed.Results:The 30 patients included 24 males and 6 females with a median age of 55.5 years. All patients underwent radical surgery after neoadjuvant therapy, 14 patients received low anterior resection, 14 patients received abdominal perineal resection, and the other 2 patients received Hartmann procedure. All patients achieved R0 resection with a median operative time 220 minutes and the median intraoperative blood loss was 200 ml. The morbidity of postoperative complications was 20% (6/30), including dysuria in 2 patients, delayed healing of perineal incision in 2 patients, intestinal obstruction in 1 patient and pelvic hemorrhage in 1 patient. The median time to first flatus after surgery was 3 days and the median postoperative hospital stay was 8 days. Postoperative pathological results showed that 15 patients (50.0%) had severe tumor regression, including 4 patients (13.3%) achieved pathological complete response (pCR), 12 patients (40.0%) had moderate tumor regression, and 3 patients (10.0%) had minor tumor regression. Twenty patients had detailed pre-treatment clinical stage, and among those 20 patients, 15 patients (75.0%) and 13 patients (65.0%) achieved downstaging of tumor T stage and N stage, respectively. Only 2 patients appeared distant metastasis, and no patient had local recurrence.Conclusions:For locally advanced rectal cancer patients, mTNT doesn′t increase the morbidity of postoperative complication and is a safe and effective treatment strategy with satisfactory short-term result.

Objective:To analyze the clinical-pathological data of patients with locally advanced rectal cancer who underwent modified total neoadjuvant therapy (TNT), and to evaluate the safety and efficacy of radical surgery after modified total neoadjuvant therapy.Methods:The clinical-pathological data of 30 locally advanced rectal cancer patients who underwent modified TNT (mTNT) followed by radical resection were retrospectively analyzed. The surgical procedure, postoperative complications, tumor regression grade, tumor downstaging and prognosis were analyzed.Results:The 30 patients included 24 males and 6 females with a median age of 55.5 years. All patients underwent radical surgery after neoadjuvant therapy, 14 patients received low anterior resection, 14 patients received abdominal perineal resection, and the other 2 patients received Hartmann procedure. All patients achieved R0 resection with a median operative time 220 minutes and the median intraoperative blood loss was 200 ml. The morbidity of postoperative complications was 20% (6/30), including dysuria in 2 patients, delayed healing of perineal incision in 2 patients, intestinal obstruction in 1 patient and pelvic hemorrhage in 1 patient. The median time to first flatus after surgery was 3 days and the median postoperative hospital stay was 8 days. Postoperative pathological results showed that 15 patients (50.0%) had severe tumor regression, including 4 patients (13.3%) achieved pathological complete response (pCR), 12 patients (40.0%) had moderate tumor regression, and 3 patients (10.0%) had minor tumor regression. Twenty patients had detailed pre-treatment clinical stage, and among those 20 patients, 15 patients (75.0%) and 13 patients (65.0%) achieved downstaging of tumor T stage and N stage, respectively. Only 2 patients appeared distant metastasis, and no patient had local recurrence.Conclusions:For locally advanced rectal cancer patients, mTNT doesn′t increase the morbidity of postoperative complication and is a safe and effective treatment strategy with satisfactory short-term result.

Objective To investigate the clinical efficacy of unilateral approach painless vertebral augmentation in the treatment of severe osteoporotic vertebral compression fractures ( OVCFs) in the critically ill patients under lateral decubitus postition. Methods A retrospective case series study was conducted to analyze 97 patients with severe vertebral fractures admitted to the Henan Provincial People's Hospital from April 2004 to January 2017. There were 27 males and 70 females, aged 59-99 years [(78. 5 ± 13. 2) years]. There were 11 patients with three-segment fracture, nine patients with two-segment fracture and 77 patients with single fracture. All patients were treated with lateral decubitus unilateral approach for painless vertebral augmentation and received postoperative rehabilitation training guided by physicians. Preoperative and intraoperative blood loss were recorded. Preoperative and postoperative respiratory rate, heart rate, systolic pressure, oxygen saturation and acute physiology and chronic health evaluation score II ( APACHE II ) , height of vertebral compression site, and injured vertebrae Cobb angle were evaluated. The visual analogue scale ( VAS) and Oswestry dysfunction index ( ODI) were assessed to define function improvement. Meanwhile, the occurrence of re-fracture and complications were recorded. Results All patients were followed up for 3-8 months [(6.3 ±2.9)months]. The operation time was (69. 2 ± 25. 9) minutes, and the amount of intraoperative bleeding was (7. 5 ± 2. 6)ml. There were no significant differences in respiratory rate, heart rate, systolic blood pressure or oxygen saturation before operation and after operation ( P > 0. 05 ) . No surgical discontinuation or deterioration occurred. The APACHE II score was (15. 2 ± 3. 7) points before operation and (8. 4 ± 0.7)points at 24 hours after operation (P <0.05). The compression height parameter of the injured vertebraewas(17.2±3.6)mmbeforesurgery,(20.4±41.3)mmatoneweekaftersurgery,and(18.8± 1.3)mm at the last follow-up (P >0. 05). The Cobb angle was (25. 6 ± 9. 3)° before operation, (20.7±2.5)° at one week after operation and (18.5±3.1)° at the last follow-up (P>0.05). The VAS score was (8. 5 ± 1. 2)points before operation, (2. 1 ± 0. 3)points at one week after operation, and (3. 2 ± 1. 1)points at the last follow-up, respectively. The VAS scores at 1 week and the last follow-up were significantly improved compared with preoperative VAS ( P<0. 05 ) , but there was no significant difference between the former two (P>0. 05). The ODI value was 39. 9 ± 3. 4 before operation, 20. 2 ± 5. 2 at one week after operation, and 17. 2 ± 2. 0 at the last follow-up . The ODI values 1 week after operation and at the last follow-up were significantly improved compared with preoperative ODI ( P <0. 05),showing improvement trend during the follow-up (P<0. 05). No re-fracture occurred during the follow-up. No serious complications such as nerve injury, pulmonary embolism or death occurred during the operation and postoperative follow-up. Conclusions The unilateral approach painless vertebral augmentation for the treatment of severe OVCFs in critically ill patients under lateral decubitus position can improve the patient's operative tolerance and satisfaction, shorten the operation time, relieve postoperative pain and promote functional recovery. It is an alternative surgical procedure for the treatment of severe OVCFs in internal medicine.

Ovarian cancer is the fifth leading cause of cancer-related death in women. 75% of ovarian cancer patients were detected at an advanced stage. At present,the disease lacks effective early screening method and the clinical therapy effect is poor,which has become a serious threat to women's health. The use of animal models of ovarian cancer is an important mean to elucidate the pathogenesis of the disease,and to screen effective diagnosis and treatment. The disease models are mainly divided into four types: spontaneous, induced, transplanted and gene intervention type. Mice, rats, hens,Mirotus Fortis and Mongolian gerbil are mainly selected to prepare animal models of ovarian cancer. Based on recent literature reports,we reviewed the preparation method of animal models of ovarian cancer and introduced the evaluation standards and main characteristics of these animal models.

Objective To investigate the role of cytokines combined with CLIF consortium organ failure score (CLIF-COFs) for predicting the occurrence of acute respiratory distress syndrome (ARDS) in for post-liver transplant for hepatitis B-related acute-on-chronic liver failure (HB-ACLF) patients.Methods From Jul.2014 to Oct.2017,there were 37 cases of HB-ACLF undergoing liver transplantation in Beijing YouAn Hospital,Capital Medical University.According to whether the patients happened ARDS or not,37 cases were divided into ARDS group (n =9) and non-ARDS group (n =28).All patients' plasma was prospectively collected immediately before liver transplantation and on the I st,3rd,5th,7th day post-liver transplantation.The serum levels of twenty-seven cytokines were determined by 200 LUMINEX liquid chip technology.Cytokines,CLIF-COFs,clinical and biochemical indexes were analyzed with logistic regression and the receiver operating characteristic (ROC) to confirm the correlation with ARDS post liver transplantation.Results There were significant differences between HB-ACLF patients between ARDS group and non-ARDS group in age and pre-transplant infection (P ＜ 0.05).The CLIF-COFs was higher in ARDS non-without than that in non-ARDS group (P =0.019).The serum levels of vascular endothelial growth factor and platelet-derived growth factor bb were lower but IL-6 was higher post transplantation in ARDS group.The COX analysis indicated that CLIF-COFs and post liver transplantation PDGF-BB were predictors of post-LT ARDS.The area under the receiver operating characteristic (AUROC) curves was 0.728 and 0.175,respectively.The area under the curve of the discriminatory power of CLIF-COFs combined with PDGF-BB was 0.913,and the maximum Youden index is 0.786.Conclusion CLIF-COFs combines with PDGF-BB can predict the occurrence of ARDS post-liver transplantation in HB-ACLF patients.

PURPOSE: Breast cancer is the most commonly occurring cancer among women worldwide, and therefore, improved approaches for its early detection are urgently needed. As microRNAs (miRNAs) are increasingly recognized as critical regulators in tumorigenesis and possess excellent stability in plasma, this study focused on using miRNAs to develop a method for identifying noninvasive biomarkers. METHODS: To discover critical candidates, differential expression analysis was performed on tissue-originated miRNA profiles of 409 early breast cancer patients and 87 healthy controls from The Cancer Genome Atlas database. We selected candidates from the differentially expressed miRNAs and then evaluated every possible molecular signature formed by the candidates. The best signature was validated in independent serum samples from 113 early breast cancer patients and 47 healthy controls using reverse transcription quantitative real-time polymerase chain reaction. RESULTS: The miRNA candidates in our method were revealed to be associated with breast cancer according to previous studies and showed potential as useful biomarkers. When validated in independent serum samples, the area under curve of the final miRNA signature (miR-21-3p, miR-21-5p, and miR-99a-5p) was 0.895. Diagnostic sensitivity and specificity were 97.9% and 73.5%, respectively. CONCLUSION: The present study established a novel and effective method to identify biomarkers for early breast cancer. And the method, is also suitable for other cancer types. Furthermore, a combination of three miRNAs was identified as a prospective biomarker for breast cancer early detection.
Area Under Curve ; Biomarkers ; Biomarkers, Tumor ; Breast Neoplasms* ; Breast* ; Carcinogenesis ; Data Mining ; Early Detection of Cancer ; Female ; Genome ; Humans ; Methods ; MicroRNAs* ; Plasma ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; Reverse Transcription ; Sensitivity and Specificity