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

BACKGROUND:The plateau environment affects the immune function and metabolic status of patients with osteomyelitis,leading to acceleration or complication of the disease process.The construction of effective and stable animal models of chronic osteomyelitis is essential for experimental studies of chronic osteomyelitis.OBJECTIVE:To establish a sheep model of chronic osteomyelitis in plateau regions for toxicity assessment and therapeutic research.METHODS:Fifteen healthy sheep were selected in this study.Sodium morrhuate and Staphylococcus aureus suspension were injected into the medullary cavity of the middle segment of the tibia to establish the chronic osteomyelitis model.General observation,body mass and temperature monitoring,blood infection index detection,radiological scoring,and microbial culture were performed for evaluation and analysis.RESULTS AND CONCLUSION:(1)Local tissue swelling and lameness of the affected leg were observed in all sheep in the early stage after modeling,accompanied by varying degrees of anorexia.A slight decrease in body mass was observed in sheep 1 week after modeling,while no significant changes in body temperature were observed.(2)The erythrocyte sedimentation rate significantly accelerated 4 days after modeling(P<0.05)and gradually returned to normal levels after 1 month.The white blood cell count showed a significant increase within 4 days after modeling and returned to normal after 1 week.The level of C-reactive protein increased significantly after modeling(P<0.05)and remained significantly higher than normal until the end of the experiment(P<0.05).(3)Fifteen sheep exhibited typical radiological manifestations of osteomyelitis,including unclear boundaries,irregular osteolytic lesions,and low-density bright absorption areas with interspersed necrotic bone fragments of increased and uneven density.Different degrees of periosteal reaction were observed in the cortex near the lesion.(4)Thirteen sheep were cultured for a single strain of Staphylococcus aureus,while two sheep were cultured for Staphylococcus aureus and Escherichia coli.These findings indicate that a reliable chronic osteomyelitis animal model of sheep tibia can be successfully established in plateau regions by injecting an appropriate amount of Staphylococcus aureus suspension into the medullary cavity of sheep,combined with local implantation of foreign cotton thread and sodium morrhuate.

BACKGROUND:The plateau environment affects the immune function and metabolic status of patients with osteomyelitis,leading to acceleration or complication of the disease process.The construction of effective and stable animal models of chronic osteomyelitis is essential for experimental studies of chronic osteomyelitis.OBJECTIVE:To establish a sheep model of chronic osteomyelitis in plateau regions for toxicity assessment and therapeutic research.METHODS:Fifteen healthy sheep were selected in this study.Sodium morrhuate and Staphylococcus aureus suspension were injected into the medullary cavity of the middle segment of the tibia to establish the chronic osteomyelitis model.General observation,body mass and temperature monitoring,blood infection index detection,radiological scoring,and microbial culture were performed for evaluation and analysis.RESULTS AND CONCLUSION:(1)Local tissue swelling and lameness of the affected leg were observed in all sheep in the early stage after modeling,accompanied by varying degrees of anorexia.A slight decrease in body mass was observed in sheep 1 week after modeling,while no significant changes in body temperature were observed.(2)The erythrocyte sedimentation rate significantly accelerated 4 days after modeling(P<0.05)and gradually returned to normal levels after 1 month.The white blood cell count showed a significant increase within 4 days after modeling and returned to normal after 1 week.The level of C-reactive protein increased significantly after modeling(P<0.05)and remained significantly higher than normal until the end of the experiment(P<0.05).(3)Fifteen sheep exhibited typical radiological manifestations of osteomyelitis,including unclear boundaries,irregular osteolytic lesions,and low-density bright absorption areas with interspersed necrotic bone fragments of increased and uneven density.Different degrees of periosteal reaction were observed in the cortex near the lesion.(4)Thirteen sheep were cultured for a single strain of Staphylococcus aureus,while two sheep were cultured for Staphylococcus aureus and Escherichia coli.These findings indicate that a reliable chronic osteomyelitis animal model of sheep tibia can be successfully established in plateau regions by injecting an appropriate amount of Staphylococcus aureus suspension into the medullary cavity of sheep,combined with local implantation of foreign cotton thread and sodium morrhuate.

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.

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.

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.

Objective To explore the clinical characteristics of hepatic sinusoidal obstruction syndrome (HSOS)related to Tusanqi (senecio chrysanthemoides)and fully recognize the severity of the disease. Methods Medical record data of patients who were diagnosed as having Tusanqi-related HSOS in the First Affiliated Hospital of Soochow University from January 2011 to May 2018 were collected and analyzed retrospectively. Results A total of 19 patients entered the study, including 12 males (63.2% ),7 females (36.8% ),and the median age was 65 (44-82 )years. All the patients mistook Tusanqi for Sanqi (Panax notoginseng),and they themselves took Tusanqi steeping in water(13 cases), decocting in water (4 cases)or soaking in wine(2 cases). The reasons for taking Tusanqi were trauma (11 cases),hypertension (4 cases of),lumbar intervertebral disc herniation(2 cases),lumbar fracture (1 cases),and prostatitis hemorrhage(1 cases). The median time of Tusanqi use was 23(5-212)days. The median time from Tusanqi initiation to onset of HSOS was 20 (5-212)days. The RUCAM score were 4 for 1 case,5 for 7 cases,6 for 5 cases,7 for 4 cases,8 for 2 cases. The patients′Child-Pugh was classified as follows:A (2 cases),B (8 cases)and C (9 cases). The types of liver injury were cholestasis in 5 cases,hepatocyte injury in 6 cases,and mixed type in 8 cases. The severity of HSOS was classified as super severe in 5 cases,severe in 4 cases,moderate in 7 cases,and mild in 3 cases. The clinical manifestations included abdominal distension,poor appetite,jaundice,hepatomegaly,ascites,and edema of both lower limbs. Laboratory abnormalities included elevated ALT,AST,TBil,and INR levels,prolonged prothrombin time,and decreased PLT and serum albumin levels. The imaging findings were mainly ascites, hepatomegaly,decreased density of liver parenchyma,uneven liver enhancemen,and unclear hepatic vein. The treatment measures included hepatoprotection,diuresis,anticoagulation,hormone therapy,improvement of microcirculation and plasmapheresis. The outcomes of the patients showed that 15 patients improved,and 4 died;and the mortality was 21.1%. Conclusions Tusanqi-related HSOS was a serious adverse reaction with decompensated liver disease as the main manifestation,poor prognosis and high mortality. Therefore, public education of safe drug use should be strengthen to avoid the misuse of Tusanqi.

Objective To explore the clinical characteristics of hepatic sinusoidal obstruction syndrome (HSOS)related to Tusanqi (senecio chrysanthemoides)and fully recognize the severity of the disease. Methods Medical record data of patients who were diagnosed as having Tusanqi-related HSOS in the First Affiliated Hospital of Soochow University from January 2011 to May 2018 were collected and analyzed retrospectively. Results A total of 19 patients entered the study, including 12 males (63.2% ),7 females (36.8% ),and the median age was 65 (44-82 )years. All the patients mistook Tusanqi for Sanqi (Panax notoginseng),and they themselves took Tusanqi steeping in water(13 cases), decocting in water (4 cases)or soaking in wine(2 cases). The reasons for taking Tusanqi were trauma (11 cases),hypertension (4 cases of),lumbar intervertebral disc herniation(2 cases),lumbar fracture (1 cases),and prostatitis hemorrhage(1 cases). The median time of Tusanqi use was 23(5-212)days. The median time from Tusanqi initiation to onset of HSOS was 20 (5-212)days. The RUCAM score were 4 for 1 case,5 for 7 cases,6 for 5 cases,7 for 4 cases,8 for 2 cases. The patients′Child-Pugh was classified as follows:A (2 cases),B (8 cases)and C (9 cases). The types of liver injury were cholestasis in 5 cases,hepatocyte injury in 6 cases,and mixed type in 8 cases. The severity of HSOS was classified as super severe in 5 cases,severe in 4 cases,moderate in 7 cases,and mild in 3 cases. The clinical manifestations included abdominal distension,poor appetite,jaundice,hepatomegaly,ascites,and edema of both lower limbs. Laboratory abnormalities included elevated ALT,AST,TBil,and INR levels,prolonged prothrombin time,and decreased PLT and serum albumin levels. The imaging findings were mainly ascites, hepatomegaly,decreased density of liver parenchyma,uneven liver enhancemen,and unclear hepatic vein. The treatment measures included hepatoprotection,diuresis,anticoagulation,hormone therapy,improvement of microcirculation and plasmapheresis. The outcomes of the patients showed that 15 patients improved,and 4 died;and the mortality was 21.1%. Conclusions Tusanqi-related HSOS was a serious adverse reaction with decompensated liver disease as the main manifestation,poor prognosis and high mortality. Therefore, public education of safe drug use should be strengthen to avoid the misuse of Tusanqi.

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.