Ulcerative colitis (UC) is a chronic inflammatory disorder with a complex etiology, characterized by intestinal inflammation and barrier dysfunction. Platycodon grandiflorus polysaccharides (PGP), the primary component of Platycodon grandiflorus, and hesperidin (Hesp), a prominent active component in Citrus aurantium L. (CAL), have both demonstrated anti-inflammatory properties. This study aims to elucidate the underlying mechanism of the synergistic effect of PGP combined with Hesp on UC, focusing on the coordinated interaction between the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. A mouse model of UC induced by dextran sulfate sodium (DSS) and a cell model using lipopolysaccharide (LPS)-induced RAW264.7/IEC6 cells were employed to investigate the in vitro and in vivo anti-inflammatory effects of PGP combined with Hesp on UC and its potential mechanism of action. The results indicated that compared to the effects of either drug alone, the combination of PGP and Hesp significantly modulated inflammatory factor levels, inhibited oxidative stress, regulated colonic mucosal immunity, suppressed apoptosis, and restored intestinal barrier function in vitro and in vivo. Further in vitro studies revealed that PGP significantly inhibited the PI3K/AKT signaling pathway, while Hesp significantly inhibited the JAK2/STAT3 signaling pathway. The use of inhibitors and activators targeting both pathways validated the synergistic effects of PGP combined with Hesp on the PI3K/AKT and JAK2/STAT3 signaling pathways. These findings suggest that PGP combined with Hesp exhibits a synergistic effect on DSS-induced colitis, potentially mediated through the phosphatase and tensin homolog (PTEN)/PI3K/AKT and interleukin-6 (IL-6)/JAK2/STAT3 signaling pathways.
Animals ; STAT3 Transcription Factor/genetics* ; Janus Kinase 2/genetics* ; Polysaccharides/administration & dosage* ; Colitis, Ulcerative/chemically induced* ; Mice ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Drug Synergism ; Male ; Hesperidin/administration & dosage* ; Platycodon/chemistry* ; Phosphatidylinositol 3-Kinases/genetics* ; Disease Models, Animal ; RAW 264.7 Cells ; Mice, Inbred C57BL

Anterior cruciate ligament(ACL)injury is caused by strong violence,which can destabilize the knee joint,cause joint cartilage degeneration,meniscus injury,and in severe cases,develop osteoarthropathy.The gold standard for the treatment of ACLR injuries at this stage is arthroscopic anterior cruciate ligament recon-struction(ACLR).In clinical practice,the LARS(Ligament advanced reinforcement system)artificial ligament made of polyethylene terephthalate(PET)as the material has a good effect in the short and medium term,but the long-term biological healing between the graft and the host bone is poor,and the real"ligamentization"requirement of the postoperative graft cannot be met.Coating-modified modification of artificial ligaments can improve their hydrophilicity and biocompatibility,which in turn can promote the healing of graft-bone tunnels.Tendon bone healing is a bone-derived progressive process from indirect insertion to direct insertion,which takes a relatively long time and is closely related to the prognosis and early rehabilitation effect of patients.This article reviews the progress of superficial modification of artificial ligaments to promote ACLR tendon bone healing.

Objective To explore the clinical effect and safety of carrellizumab combined with albumin-bound paclitaxel on the treatment of patients with locally advanced esophageal cancer.Methods Ninety-eight patients with locally advanced esophageal cancer were randomly divided into the study group and the reference group,with 49 cases in each group.The reference group was treated with albumin-bound paclitaxel,while the study group was treated with camrelizumab+albumin-bound paclitaxel.After treatment,the overall efficacy was evaluated,and the disease control rate was calculated.Serum tumor markers[high mobility group protein B1(HMGB1),squamous cell carcinoma associated antigen(SCCA)],PD-1 and PD-L1 levels were detected by enzyme-linked immunosorbent assay(ELISA)before and after treatment.Immunohistochemistry was used to detect the microvascular density(MVD)and the expression levels of PD-1 and PD-L1 in esophageal carcinoma tissue.The percentages of CD3+,CD4+and CD8+cells were detected by flow cytometry.Patients were followed up and adverse reactions and survival were recorded.Results The disease control rate was higher in the study group than that of the control group(P＜0.05).There were no significant differences in all indexes between the groups before treatment(P＞0.05).After treatment,HMGB1 level,SCCA level,MVD,serum PD-1 level and tumor tissue high expression rate of PD-1 were all decreased in the two groups,while serum PD-L1 level,PD-L1 high expression rate and percentages of CD3+,CD4+and CD8+cells were all increased(P＜0.05).Except there was no significant difference in MVD between groups,the other indexes were significantly changed in the study group compared with the control group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).The progression-free survival rate was higher in the study group than that of the control group(P＜0.05).Conclusion Carrellizumab combined with albumin-bound paclitaxel in the treatment of locally advanced esophageal cancer can help control lesion progression and inhibit angiogenesis,with good safety.

L-homophenylalanine (L-HPA) is an important non-natural amino acid that has been used as a key intermediate for the synthesis of Puli drugs for the treatment of hypertension. At present, L-HPA is synthesized using chemical methods, which has the disadvantages of expensive raw materials, tedious steps and serious pollution. Therefore, researchers have conducted in-depth research on the enzymatic production of L-HPA. This review summarizes the research progress on the enzymatic synthesis of L-HPA, including the dehydrogenase process, the transaminase process, the hydantoinase process, and the decarboxylase process, with the hope to facilitate the industrial production of L-HPA.
Amino Acids ; Environmental Pollution ; Industry ; Protein Biosynthesis

Objective:To study the timing of radiofrequency ablation (RFA) in treatment of complicated pyogenic liver abscesses (PLA).Methods:A retrospective analysis was performed on 49 patients with complicated PLA who were treated with the RFA-based treatment modality from August 2010 to January 2020 at Beijing Chaoyang Hospital, West Campus, Capital Medical University, Institute of Hepatobiliary, Pancreas and Spleen Surgery and the Second Hospital, Binzhou. The patients were divided into the early RFA group (≤ 72 h, n=27) and the delayed RFA group (>72 h, n=22) according to the timing of RFA. RFA was guided by laparoscopy combined with Ultrasound or CT. The safety and effective rates of RFA, and the total expenses were evaluated. Results:All patients in both the early and the delayed RFA groups were successfully cured (100%). No serious complications, including biliary leakage and massive hemorrhage, happened in the 2 groups. Significantly longer operating time and hospital stays [(8.1±1.6)d vs. (9.5±1.5)d], and higher hospital costs [(3.4±0.2) ten thousand yuan vs. (3.8±0.4) ten thousand yuan] were found in the delayed RFA group when compared with the early RFA group ( P<0.05). Conclusion:RFA treatment of complicated PLA should be completed within 72 hours of onset of PLA.

To summarize the breeding and identification of Wuzhishan miniature pig models with α-l,3-galactosyltransferase (GGTA1) gene-knockout (GTKO).Methods The breeding and reproduction perform of GTKO Wuzhishan miniature pigs were assessed and the quantity of piglets was counted.The GTKO Wuzhishan miniature pig models with GGTA1gene knockout were validated by polymerase chain reaction(PCR).The αGal phenotype of peripheral blood mononuclear cells (PBMC) in human,wild-type Wuzhishan miniature pigs and GTKO Wuzhishan miniature pigs was detected by fluorescent microscope and flow cytometry.Routine blood test parameters were statistically compared between the GTKO and wild-type Wuzhishan miniature pigs.Results The inheritance of GGTA1 genotype complied with Mendel's law.Flow cytometry detected no fluorescent expression of PBMC in GGTA1-/-pig models,which were consistent with the genotype identification results.The mean piglets of the primiparous GTKO Wuzhishan miniature pigs were (6.8±1.8) and (8.3±2.2) for the multiparous Wuzhishan miniature pigs.No statistical significance was noted in routine blood test parameters between the GTKO and wild-type Wuzhishan miniature pigs (all P＞0.05).Conclusions Stable inheritance and normal reproductive capacity are observed in two generations of Wuzhishan miniature pigs continuously.GTKO Wuzhishan miniature pig is a reliable donor for heterogeneous organ transplantation.

Objective To assess the clinical effect of lumboperitoneal shunting (LPS) on communicating hydrocephalus.Methods An retrospectively study was conducted on communicating hydrocephalus patients who were hospitalized from Sep.2009 and Dec.2013 at the No.174th Hospital of Chinese People's Liberation Army.All patients were underwent the LPS.All patients were with difference degrees of coma,and lumbar punctured for continued cerebrospinal fluid extended drainage before LPS.The change of disturbance of consciousness and the complications of LPS were assessed.Results There were 12 patients with communicating hydrocephalus.Of them,7 cases were underwent routine lumboperitoneal shunts,and 5 cases were experienced adjustment valve.After the LPS operation,3 patients were awakened from the coma,and 8 patients were improved in terms of consciousness and the decompression pressure of skull window as well as decreased enlarged lateral ventricles in pre-operation by CT.As for another 1 patient,the lumboperitoneal catheter had been slipped into the peritoneal cavity after 2 months of operation.There were no complications of infection,intracranial hemorrhages,obstruction of catheter and epilepsy.Conclusion The LPS should be the first selection of those patients who suffered from communicating hydrocephalus without trouble in spine and abdomen.A positive response to pre-operative continuing cerebrospinal fluid extend drainage is good prediction factor for surgical results of LPS.

Objective Introduce a technique for creating 3-dimensional (3D) brain models of subdural electrodes , ideal for demonstrating the space-relationship of seizure localization and eloquent cortices , and discuss its usefulness for presurgical evaluation of epileptic patients. Methods Patients with medically intractable epilepsy were underwent a thorough preoperative MR brain scan including a T1-weighted high-resolution 3D sequence. Intraoperative photographs were taken with the digital camera. After the surgical implantation of subdural electrodes for epileptic zone localization , the thin-slice CT scan of the electrodes were taken and coregistered to preoperative brain 3D MR images in the Medtronic StealthMerge software environment. After the iEEG monitoring , multiple habitual seizures were recorded , eloquent areas were also identified by electrical stimulation of the cortex. The epileptic zone and the eloquent areas were marked on the subdural electrodes respectively. Then, 3D tessellations of the epileptic zone and the eloquent areas were rendered. Results Six patients (4 male, 2 female) were enrolled in this study. The mean time of iEEG monitoring was 13.7 days. After the coregistration of postoperative CT with preoperative 3D MRI , the 3D stereoscopic reconstruction provided an accurate representation of the implanted electrodes with highly detailed visualization of the underlying anatomy. The visual comparison between 3D reconstructions and intraoperative photographs indicated a good correspondence. The patients were followed for 3 to 6 months after the secondary operation , and had continuing improvement in seizure control. Conclusions The results indicate that the 3D reconstruction of subdural electrodes can reveal the precise localization of subdural electrodes , and can be useful for the presurgical evaluation of epileptic patients.

To investigate whether chemically modified non-anticoagulation heparin derivate (periodate oxidation/borohydride reduction-modified heparin (OR-heparin)) could inhibit high glucose-induced human mesangial cell apoptosis and to explore its possible mechanism.Methods:Mesangial cells were exposed to high glucose or high glucose with OR-heparin for 24 h.Apoptosis was evaluated by Hoechst 33258 staining and Fluorescent activated cell sorting analysis.The expressions of apoptosis-related proteins ( p53,Bcl-2,Bax,cytosolic cytochrome C) were determined by Western blotting.NF-kB translocation was observed under fluorescence microscopy by using Cy3-1abeled antibody.Caspase-3 activity was detected by colorimetry.Results:OR-heparin significantly inhibited high glucose-induced mesangial cell apoptosis and the expression of apoptosis-related proteins.It also blocked NF-kB translocation induced by high glucose.Conclusion:OR-heparin inhibits high glucose-induced mesangial cell apoptosis through inhibiting the expression of apoptosis-related proteins and it may be due to the blockage of the translocation of NF-kB.