Role and mechanism of esketamine in improving postoperative cognitive dysfunction in aged mice through the TLR4/MyD88/p38 MAPK pathway.

Postoperative cognitive dysfunction (POCD) is a significant concern for the elderly population worldwide. This study explored the effects of esketamine on aged mice with POCD and investigate its mechanism of action involving the TLR4/MyD88/MAPK pathway. We administrated esketamine, along with lipopolysaccharide or anisomycin, to the aged POCD mouse models. We assessed their cognitive function using the Morris water maze test. Additionally, we evaluated histopathological changes/neuronal apoptosis in the mouse hippocampal CA1 area through HE/TUNEL stainings. Furthermore, we measured IL-1ß/IL-6/TNF-α/TLR4/MyD88/MAPK (p-p38/p38) levels in mouse hippocampal tissues using ELISA/RT-qPCR/Western blotting. Lastly, we analyzed the interaction between TLR4 and MyD88 using a co-immunoprecipitation assay. Our findings showed that esketamine effectively mitigated POCD in aged mice. This was evident from the improved cognitive performance observed in the Morris water maze test, characterized by reduced escape latency/increased number of platform crossing/a higher percentage of time spent in the target quadrant. Furthermore, esketamine exhibited a protective effect against neuronal apoptosis and reduced the levels of inflammatory factors. These findings suggest that esketamine exerts an anti-inflammatory effect by downregulating TLR4/MyD88, thereby attenuating the inflammatory response associated with POCD. Additionally, esketamine suppressed the p38 MAPK pathway by inhibiting the TLR4/MyD88 signaling cascade. Esketamine demonstrated its efficacy in improving postoperative inflammation and cognitive impairment in aged mice by inhibiting the TLR4/MyD88 pathway. The activation of p38 MAPK signaling diminished the beneficial effects of esketamine in aged POCD mice. Collectively, the underlying mechanism of esketamine in mitigating POCD in aged mice involves the suppression of the TLR4/MyD88/p38 MAPK pathway.

Sarcomatoid intrahepatic cholangiocarcinoma with good patient prognosis after treatment with Huaier granules following hepatectomy: A case report.

BACKGROUND: Sarcomatoid intrahepatic cholangiocarcinoma (SICC) is an extremely rare and highly invasive malignant tumor of the liver. The precise pathologic mechanism of SICC has not been clearly identified, and the prognosis is very poor. The effectiveness of the treatment strategy of radical hepatectomy combined with Huaier granules has not yet been reported. CASE SUMMARY: The patient was a 69-year-old male who presented with intermittent right upper abdominal pain for one month and 4-pound weight loss before admission. Abdominal magnetic resonance imaging and magnetic resonance cholangiopancreatography showed multiple stones in the bile ducts accompanied by dilatation of the intrahepatic and extrahepatic bile ducts. The preoperative diagnoses were right intrahepatic bile duct stones and extrahepatic bile duct stones; thus, surgical resection was performed. Choledochoscopy showed that the bile duct wall of the right anterior lobe was thickened, and a mass was visible in the duct. Then, a biopsy was performed, and rapid frozen-section biopsy analysis indicated that the tumor was malignant. The final diagnosis was SICC (T1aN0M0). Huaier granules were taken by the patient as anticancer therapy after surgery. The patient attended follow-up for 72 mo with no tumor recurrence or metastasis. CONCLUSION: Sarcomatous intrahepatic cholangiocarcinoma is an extremely rare, aggressive malignancy, and the diagnostic gold standard is pathological diagnosis. We reported the first case of successful treatment with Huaier granules as anticancer therapy after surgery, which indicated that Huaier granules are safe and effective. Further studies are needed to study the anticancer molecular mechanisms of Huaier granules in sarcomatous intrahepatic cholangiocarcinoma.

COVID-19 or treatment associated immunosuppression may trigger hepatitis B virus reactivation: A case report.

BACKGROUND: Since the initial recognition of coronavirus disease 2019 (COVID-19) in Wuhan, this infectious disease has spread to most areas of the world. The pathogenesis of COVID-19 is yet unclear. Hepatitis B virus (HBV) reactivation occurring in COVID-19 patients has not yet been reported. CASE SUMMARY: A 45-year-old hepatitis B man with long-term use of adefovir dipivoxil and entecavir for antiviral therapy had HBV reactivation after being treated with methylprednisolone for COVID-19 for 6 d. CONCLUSION: COVID-19 or treatment associated immunosuppression may trigger HBV reactivation.

Multi-parameter ultrasound based on the logistic regression model in the differential diagnosis of hepatocellular adenoma and focal nodular hyperplasia.

BACKGROUND: Focal nodular hyperplasia (FNH) has very low potential risk, and a tendency to spontaneously resolve. Hepatocellular adenoma (HCA) has a certain malignant tendency, and its prognosis is significantly different from FNH. Accurate identification of HCA and FNH is critical for clinical treatment. AIM: To analyze the value of multi-parameter ultrasound index based on logistic regression for the differential diagnosis of HCA and FNH. METHODS: Thirty-one patients with HCA were included in the HCA group. Fifty patients with FNH were included in the FNH group. The clinical data were collected and recorded in the two groups. Conventional ultrasound, shear wave elastography, and contrast-enhanced ultrasound were performed, and the lesion location, lesion echo, Young's modulus (YM) value, YM ratio, and changes of time intense curve (TIC) were recorded. Multivariate logistic regression analysis was used to screen the indicators that can be used for the differential diagnosis of HCA and FNH. A ROC curve was established for the potential indicators to analyze the accuracy of the differential diagnosis of HCA and FNH. The value of the combined indicators for distinguishing HCA and FNH were explored. RESULTS: Multivariate logistic regression analysis showed that lesion echo (P = 0.000), YM value (P = 0.000) and TIC decreasing slope (P = 0.000) were the potential indicators identifying HCA and FNH. In the ROC curve analysis, the accuracy of the YM value distinguishing HCA and FNH was the highest (AUC = 0.891), which was significantly higher than the AUC of the lesion echo and the TIC decreasing slope (P < 0.05). The accuracy of the combined diagnosis was the highest (AUC = 0.938), which was significantly higher than the AUC of the indicators diagnosing HCA individually (P < 0.05). This sensitivity was 91.23%, and the specificity was 83.33%. CONCLUSION: The combination of lesion echo, YM value and TIC decreasing slope can accurately differentiate between HCA and FNH.

Postoperative local incision analgesia for acute pain treatment in patients with hepatocellular carcinoma.

OBJECTIVE: The present study aimed to investigate the analgesic effect and safety of using local incision analgesia to treat acute postoperative pain in patients with hepatocellular carcinoma (HCC). METHOD: A cohort of 60 patients undergoing liver cancer resection was randomly divided into three groups (n=20 per group): local incision analgesia (LIA) group, which received local infiltration with ropivacaine combined with a postoperative analgesia pump; intravenous patient-controlled analgesia (PCA) group, which received fentanyl intravenous analgesia postoperatively; and the control group, which received tramadol hydrochloride injection postoperatively according to the NRS scoring system. The postoperative analgesic effect in each group was compared and tumor recurrence (survival) was analyzed using the Kaplan-Meier method. RESULTS: NRS scores, rate of analgesic usage, ambulation time (h) and intestinal function recovery time (h) were significantly reduced in LIA group compared with the control group at each postoperative time point (6, 12, 24 and 48 hours; p<0.05). Additionally, the NRS scores of LIA patients at 12 hours post-surgery was significantly reduced compared with PCA group (p<0.05), and the occurrence of postoperative adverse events in LIA group was significantly lower than that in PCA group (p<0.05). Survival analysis demonstrated that the mean survival time (tumor recurrence) was significantly increased in LIA group compared with the control group (χ2=4.749; p=0.029). CONCLUSION: Local incision analgesia improves the analgesic effect, causes fewer adverse reactions and increases postoperative survival time. Our study demonstrated that local incision analgesia is a safe and effective method of postoperative pain management following hepatectomy.

Postoperative local incision analgesia for acute pain treatment in patients with hepatocellular carcinoma

Summary Objective: The present study aimed to investigate the analgesic effect and safety of using local incision analgesia to treat acute postoperative pain in patients with hepatocellular carcinoma (HCC). Method: A cohort of 60 patients undergoing liver cancer resection was randomly divided into three groups (n=20 per group): local incision analgesia (LIA) group, which received local infiltration with ropivacaine combined with a postoperative analgesia pump; intravenous patient-controlled analgesia (PCA) group, which received fentanyl intravenous analgesia postoperatively; and the control group, which received tramadol hydrochloride injection postoperatively according to the NRS scoring system. The postoperative analgesic effect in each group was compared and tumor recurrence (survival) was analyzed using the Kaplan-Meier method. Results: NRS scores, rate of analgesic usage, ambulation time (h) and intestinal function recovery time (h) were significantly reduced in LIA group compared with the control group at each postoperative time point (6, 12, 24 and 48 hours; p<0.05). Additionally, the NRS scores of LIA patients at 12 hours post-surgery was significantly reduced compared with PCA group (p<0.05), and the occurrence of postoperative adverse events in LIA group was significantly lower than that in PCA group (p<0.05). Survival analysis demonstrated that the mean survival time (tumor recurrence) was significantly increased in LIA group compared with the control group (χ2=4.749; p=0.029). Conclusion: Local incision analgesia improves the analgesic effect, causes fewer adverse reactions and increases postoperative survival time. Our study demonstrated that local incision analgesia is a safe and effective method of postoperative pain management following hepatectomy.

Co-expression of CXCL8 and HIF-1α is associated with metastasis and poor prognosis in hepatocellular carcinoma.

Hypoxia inducible factor-1α (HIF-1α), induces cytokines such as CXCL8 and tumor dissemination, chemo- and radio-resistance. We analyzed correlation between HIF-1α and CXCL8 levels, tumor characteristics and overall survival in 102 hepatocellular carcinoma (HCC) patients. Levels of HIF-1α and CXCL8 were increased in HCC tissues and cell lines. Patients with high levels of HIF-1α and CXCL8 had worse outcome and poorer prognosis than those with lower levels. Co-overexpression of HIF-1α and CXCL8 was an independent negative prognostic factor for overall and disease-free survival. HIF-1α silencing and CXCL8 siRNA decreased migration under hypoxic conditions in vitro. Hypoxia-induced activation of AKT/mTOR/STAT3 pathways was reversed by depletion of CXCL8. We conclude that HIF-1α and CXCL8 induce HCC progression and metastasis, associated with activation of AKT/mTOR/STAT3. Co-expression of HIF-1α and CXCL8 is a prognostic marker and a potential therapeutic target in HCC.