Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice.

CONTEXT: Aryl hydrocarbon receptor (AhR) agonists are potential therapeutic agents for ulcerative colitis (UC). Indirubin (IDR), which is a natural AhR ligand approved for leukemia treatment, ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the therapeutic mechanisms of IDR are unknown, limiting its application. OBJECTIVE: This study explores the therapeutic mechanisms of IDR in DSS-induced colitis using transcriptomic analysis. MATERIALS AND METHODS: Male BALB/c mice were categorized to six groups: normal, DSS model (2% DSS), IDR treatment (10, 20 and 40 mg/kg), and sulfasalazine (520 mg/kg) groups. The drugs were intragastrically administered for 7 consecutive days. The disease activity index (DAI) was recorded. After euthanasia, the colon length was measured, and histopathological examination, immunohistochemistry staining using F4/80, and colonic transcriptomic analysis were conducted. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB) were conducted to verify our findings. RESULTS: Compared with DSS, IDR treatment decreased the DAI score by 64.9% and increased colon length by 26.2%. Moreover, it alleviated mucosal injury and reduced macrophage infiltration. Transcriptomic analysis identified several downregulated genes (Igkvs and Nlrp3), as well as Nlrp3/Il1ß and hemoglobin gene networks, after IDR treatment. The abundances of NF-κB p65, NLRP3, IL-1ß, and HBA decreased by 69.1, 59.4, 81.1, and 83.0% respectively, after IDR treatment. DISCUSSION AND CONCLUSION: Apart from the well-documented NF-κB signalling pathway, IL-17A, and NLRP3-IL-1ß, the suppression of haemoglobin-induced lipid peroxidation could be a previously unknown mechanism of IDR. Our study can help improve its application for UC treatment.

Sex and age differences in chronic postoperative pain among patients undergoing thoracic surgery: a retrospective cohort study.

Background: The effect of sex and age on chronic post-thoracic surgical pain (CPTP) at rest and with activity remains unclear. The main purpose of this study was to investigate the relationship between the incidence of chronic postoperative pain (at rest and with activity) and sex/age differences. Methods: This was a single-center retrospective study that included adult patients who had undergone elective thoracic surgery. Patients were divided into two groups based on sex. Demographic and perioperative data were collected, including age, sex, education level, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) physical status, and medical history (hypertension, diabetes mellitus). Chronic postoperative pain data were collected by telephone follow-up. Results: Among the 3,159 patients enrolled, 1,762 were male, and 1,397 were female. After creating a matched-pairs cohort, 1,856 patients were analyzed. The incidence of CPTP at rest was 14.9% among males and 17.8% among females (p = 0.090). The incidence of CPTP with activity was 28.4% among males and 35.0% among females (p = 0.002). We analyzed three different models after propensity matching to validate the stability of the prediction model between sex and CPTP, and female sex was a significant predictor of CPTP with activity 3 months after surgery. Further analysis showed that females in the 45-55-year-old age group were more prone to develop CPTP. Conclusion: Females have a higher incidence of chronic postoperative pain with activity after thoracic surgery. Females in the 45-55-year-old age group are more prone to develop CPTP than females in other age groups.

Effects of preoperative current smoking on chronic postsurgical pain in thoracic surgery: a retrospective cohort study.

OBJECTIVE: This study aimed to investigate the effect of preoperative current smoking on chronic postsurgical pain in patients who underwent thoracic surgery. METHODS: A total of 5,395 patients aged over 18 years old who underwent thoracic surgery from January 2016 to March 2020 in Henan Provincial People's Hospital were enrolled. Patients were divided into two groups: the smoking group (SG group) and the nonsmoking group (NSG group). Propensity score matching was utilized to eliminate the influence of confounding factors, and a multivariable logistic regression model was established to determine the effect of preoperative current smoking on chronic postsurgical pain. The dose-response relationship between the smoking index (SI) and chronic postsurgical pain at rest was analyzed using a restricted cubic spline curve. RESULTS: In a matched cohort of 1028 patients, the incidence of chronic pain at rest was 13.2% in the smoking group and 19.0% in the nonsmoking group (P = 0.011). Three different models were used to verify the stability of the model between preoperative current smoking and chronic postsurgical pain. A regression model was established to determine the influence of different smoking indexes (SIs) on chronic postsurgical pain. The incidence of chronic pain at rest was lower in patients with SI ≥400 before thoracic surgery than in patients whose SI was less than 400. CONCLUSIONS: A relationship between the preoperative current smoking index and chronic postsurgical pain at rest was observed. The incidence of chronic postsurgical pain at rest was lower in patients whose SI was greater than 400.

Intracardiac, pulmonary cement embolism in a 67-year-old female after cement-augmented pedicle screw instrumentation: A case report and review of literature.

BACKGROUND: We report a case of Intracardiac, pulmonary, and intravenous cement embolism after cement-augmented pedicle screw instrumentation in treating spondylolisthesis underlying osteoporotic bone, which was successfully managed by conservative treatment. We describe the treatment and outcome of the patient, hoping to shed light on the management of bone cement embolism. CASE SUMMARY: A 67-year-old female suffered from progressive low back pain and numbness in lower extremities for 30 years. She was diagnosed with L4 and L5 spondylolisthesis, spinal stenosis, and osteoporosis. The patient underwent spinal canal decompression, an interbody fusion of L4/5 and L5/S1, cement-augmented pedicle screw instrumentation in L4-L5 segments, and regular pedicle screw in S1 segments. Three days postoperatively, a sudden drop in oxygen saturation occurred. Computerized tomography scan confirmed Intracardiac, pulmonary, and intravenous embolism. The patient was treated conservatively by continuous low-flow oxygen inhalation, anti-coagulation, and antibiotic therapy for 1 mo and continued anticoagulation treatment for 6 mo. The patient showed no further symptoms in a 30-mo follow-up. CONCLUSION: Intracardiac, pulmonary cement embolism after cement-augmented pedicle screw instrumentation is extremely rare. Careful clinical and radiographic evaluation is required in multiple sites of bone cement embolism. Conservative treatment may be a primary consideration in scattered emboli without life-threatening conditions, but a clinical decision should be made on an individualized basis.

Depression in patients with chronic hepatitis B and cirrhosis is closely associated with the severity of liver cirrhosis.

Depression in patients with chronic hepatitis B (CHB) can affect the quality of life, disease diagnosis and case fatality rate. The aim of this study was to explore depression in patients with CHB and cirrhosis, and the effect of the severity of liver cirrhosis on the depressive emotional state. The depressive emotional state was investigated using the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) in 114 patients with CHB and cirrhosis, comprising 42 cases classified as Child-Pugh grade (CPG)-A, 38 cases classified as CPG-B and 34 cases classified as CPG-C at a single hepatology center. Patients with mood disorders accounted for 33.33% of the 114 cases with CHB and liver cirrhosis and comprised 10 cases of CPG-A, 12 cases of CPG-B and 16 cases of CPG-C classification. The results shows that HAMA and HAMD scores of patients in the CPG-C group were significantly higher than those in the CPG-A group (P<0.01), but not significantly higher than those in the CPG-B group (P>0.05). The incidence rate of mood disorders in the CPG-C group was significantly higher than that in the CPG-B group (P=0.0336), and the incidence rate of mood disorders was higher in the CPG-B group compared with the CPG-A group, but the difference was not statistically significant (P=0.4370). The incidence rate of mood disorders in patients in the CPG-A group was significantly lower than that in the CPG-C group (P=0.0078). The study shows that a considerable proportion of patients with liver cirrhosis have mood disorders, and the depression rates of CHB-infected patients with liver cirrhosis are closely associated with the severity of the cirrhosis.

[Inhibitory effect of inositol hexaphosphate on proliferation of LNCaP cells and its relation to IGFBP 3 expression].

OBJECTIVE: To investigate the effect of inositol hexaphosphate (IP6) on proliferation of human prostate carcinoma LNCaP cells and its relation to insulin-like growth factors binding protein-3 (IGFBP-3) expression. METHODS: The siRNA technology was used to silence the IGFBP-3 gene in LNCaP cells. LNCaP cells and IGFBP-3 gene silenced LNCaP cells were exposed to IP6 for 24 h. Cell viability was measured by MTT assay; cell cycle arrest and cell apoptosis were detected by flow cytometry. The expression levels of IGFBP-3 and Bcl-2 mRNA and protein were analyzed by real-time quantitative RT-PCR and Western blotting, respectively. RESULTS: The proliferation of LNCaP cells was be inhibited by IP6 in a dose dependent manner. After exposure to IP6 for 24 h, the cell viability in LNCaP cells and siRNA-treated LNCaP cells was 53.2%±11.6% and 82.3%±10.9%, respectively (P<0.05). After treatment of 1.5 mmol IP6，the apoptosis rate of LNCAP cells and siRNA-treated LNCAP cells was 40.48%±13.21% and 30.43%±10.65%, respectively (P<0.05). The proportion of G1 and G2 phase in LNCAP cells was 70.58%±8.25% and 5.64%±1.23%，after IP6 treatment the percentage of G1 phase cells decreased to 48.66%±11.23% and G2 phase cells increased to 31.11%±9.68%. However, for siRNA treated LNCAP cells, the proportion of G1 phase cells was 58.25%±12.36% and G2 phase cells was 23.85%±12.45%. Higher expression of IGFBP-3 and lower expression of Bcl-2 in LNCaP cells treated with IP6 were found at both mRNA and protein levels. IP6 treatment enhanced IGFBP-3 mRNA expression by 2.21±0.15 folds. In the contrast, expression of Bcl-2 mRNA decreased by 0.69±0.03 folds. Meanwhile, after IGFBP- gene silence Bcl-2 expression was not decreased. CONCLUSION: IP6 can inhibit the proliferation of LNCaP cells, which may be associated with the changes of IGFBP-3 level through Bcl-2 expression.

Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B: short-term and long-term outcomes.

UNLABELLED: Our study aimed to investigate the short-term efficacy and long-term prognosis of liver failure patients caused by hepatitis B after a single transplantation with autologous marrow mesenchymal stem cells (MMSCs). A total of 527 inpatients with liver failure caused by hepatitis B were recruited and received the same medical treatments, among whom 53 patients underwent a single transplantation with autologous MMSCs. A total of 105 patients matched for age, sex, and biochemical indexes, including alanine aminotransferase (ALT), albumin, total bilirubin (TBIL), prothrombin time (PT), and Model for End-Stage Liver Disease (MELD), comprised the control group. A total of 120 mL of bone marrow was obtained from each patient and then diluted and separated. Then, the MMSC suspension was slowly transfused into the liver through the proper hepatic artery. The success rate of transplantation was 100%, without serious side effects or complications. Levels of ALB, TBIL, and PT and MELD score of patients in the transplantation group were markedly improved from 2-3 weeks after transplantation, compared with those in the control group. At 192 weeks of follow-up, there were no dramatic differences in incidence of hepatocellular carcinoma (HCC) or mortality between the two groups. Additionally, there were no significant differences in the incidence of HCC or mortality between patients with and without cirrhosis in the transplantation group. CONCLUSION: Autologous MMSC transplantation is safe for liver failure patients caused by chronic hepatitis B. Short-term efficacy was favorable, but long-term outcomes were not markedly improved. In respect to several parameters, this method is preferable for patients with liver cirrhosis and may have potential for reducing their incidence of HCC and mortality.

Human bone marrow mesenchymal stem cells are resistant to HBV infection during differentiation into hepatocytes in vivo and in vitro.

Hepatocyte-like cells induced from bone marrow mesenchymal stem cells (BMSCs) recover liver function in animal models with liver failure. Our initial findings revealed that human BMSCs improved liver function in hepatitis B patients with end stage liver disease. However, the susceptibility of BMSCs to HBV infection during induction toward hepatocytes remains unknown. We have assessed whether BMSCs-derived hepatocyte-like cells can function like liver cells and be infected by HBV. A new and efficient way to direct the differentiation of BMSCs into functional hepatocytes was developed. BMSCs obtained from hepatitis B patients were induced to differentiate into hepatocytes through exposure to HGF, FGF-4, and EGF. After 6 days of exposure, BMSCs-derived hepatocyte-like cells that expressed a subset of hepatic genes and showed hepatic functions were obtained. HBV was used to infect the differentiated cells, and subsequently these cells were assayed for the presence of HBeAg, HBsAg, and HBV DNA. BMSCs proved resistant to HBV infection, both in vitro and during differentiation into hepatocytes in vitro. This demonstrates that BMSCs are resistant to HBV infection. BMSCs are viable for transplantation and should facilitate further research exploring the in vivo HBV-resistance of the hepatocytes derived from BMSCs after transplantation, a characteristic that could form the basis for hepatocyte transplantation.

Characterization and hepatogenic differentiation of mesenchymal stem cells from human amniotic fluid and human bone marrow: a comparative study.

Since stem cells can differentiate into hepatocyte, stem cell-based therapy becomes a potential alternative treatment for terminal liver diseases. However, an appropriate source of human mesenchymal stem cells (hMSCs) for hepatocytes has not yet been clearly elucidated. The aim of the present study was to investigate the in vitro biological characterization and hepatic differentiation potential of human amniotic fluid-derived mesenchymal stem cells (AF-hMSCs) and human bone marrow-derived mesenchymal stem cells (BM-hMSCs). Our results show that AF-hMSCs possess higher proliferation and self-renewal capacity than BM-hMSCs. Cytogenetic studies indicate that AF-hMSCs are as genetically stabile as BM-hMSCs. Following incubation with specific hepatogenic agents, AF-hMSCs showed a higher hepatic differentiation potential than BM-hMSCs. Expression of several liver-specific markers was significantly greater in AF-hMSCs than in BM-hMSCs, as shown by real time RT-PCR and immunofluorescence (IF). In conclusion, AF-hMSCs possess superior potential for hepatic differentiation, making them more suitable for diverse terminal liver diseases.

[Effect of Suanzaoren decoction on acute hepatic failure in mice].

OBJECTIVE: To investigate the effect of Suanzao nacute hepatic failure in mice. METHOD: Acute liver failure was induced in male Kunming strain mice by enterocoelia injecting the animals with D-Gal-N and LPS. The mice in treatment groups were given corresponding drug 2 h before administration of D-Ga1-N and LPS, and the mice in control group were given the same dose of distilled water. The 24 h survival rate, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels were compared. Serum the levels of TNF-alpha and IL-1 and the levels of SOD, MDA, GR, GSH, NO and NOS in the liver were determined. RESULT: Treatment with suanzaoren decoction could increase the survival rate and improve the liver histological feather. Suanzaoren decoction inhibited the serum the levels of ALT, AST, TNF-alpha and IL-1, and reduced the levels of MDA, NO and NOS and increased the levels of GR and SOD in the liver. CONCLUSION: Treatment with Suanzaoren decoction can suppress the D-Gal-N/LPS-induced acute hepatic failure. It may be the mechanism that Suanzaoren decocotion regulate the production of inflammatory cytokines and free radicals.

[Clinical observation on auxiliary treatment with suanzaoren decoction for chronic severe hepatitis].

OBJECTIVE: To investigate the curative effect and safety of auxiliary treatment with Suanzaoren Decoction (SZRD) on patients with chronic severe hepatitis (CSH). METHODS: Sixty patients, with the diagnosis in accordance with the diagnostic criterion of CSH, were assigned to the treated group and the control group, 30 in each group. Patients in the control group were treated with comprehensive therapy including symptomatic supportive treatment, anti-infective therapy and artificial liver plasmapheresis etc., while those in the treated group were orally taken SZRD additionally. Patients' condition of sleeping and changes of total bilirubin (TBIL), prothrombin activity (PTA), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) were observed before and after treatment, and the adverse reactions were observed as well. RESULTS: The sleeping status were significantly improved in the treated group after treatment, and the serum levels of TBIL, TNF-alpha and IL-1 were significantly decreased. The improvement rate was 66.7% (20/30) and significantly higher than that (40.0%, 12/30) in the control group. CONCLUSION: SZRD can significantly improve the sleeping status of CSH patients, alleviate the hepato-cellular injury by inflammatory cytokines and without obvious adverse reaction.

[Effect of diazepam and modafinil on acute hepatic failure in mice].

OBJECTIVE: To investigate the effect of diazepam and modafinil on acute hepatic failure in mice. METHODS: Acute liver failure was induced in male Kunming strain mice by enterocoelia injecting the mice with D-GalN and LPS . The mice in the treatment groups were given corresponding drug 2 h before the administration of D-GalN and LPS, and the mice in the control group were given the same dose of distilled water. The 24-hour survival rate, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were compared. Serum levels of TNF-alpha and IL-1 and the levels of SOD, MDA, GR, GSH, NO and NOS in the liver were determined. RESULTS: Treatment with diazepam increased the survival rate and improved liver histological feature. Diazepam inhibited the serum levels of ALT, AST, TNF-alpha and IL-1, and reduced levels of MDA, NO and NOS and increased levels of GR and SOD in the liver. Modafinil decreased liver histological feature, increased the serum levels of ALT, AST, TNF-alpha and IL-1, increased level of MDA, and inhabited levels of SOD and GR in the liver. CONCLUSION: Treatment with diazepam may suppress the D-GalN/LPS-induced acute hepatic failure and modafinil may facilitate the acute hepatic failure.