Safety and Effectiveness Analysis of Different Surgical Methods for Intrahepatic Bile Duct Stones.

BACKGROUND: Intrahepatic bile duct stones, a prevalent condition within hepato-biliary diseases, present a considerable challenge due to the high rates of recurrence, complications, and difficulty in treatment. Selecting an optimal surgical approach is vital for effective stone clearance and minimizing patient morbidity. While laparoscopic hepatectomy and percutaneous transhepatic choledochoscopy are established modalities, their comparative efficacy and safety profiles necessitate further investigation to inform clinical decision-making. OBJECTIVE: To explore the effectiveness and safety of different surgical methods for intrahepatic bile duct stones.  Methods: The clinical data of 65 patients with intrahepatic bile duct stones admitted to Nanchong Central Hospital, China, from January 2021 to January 2022 were retrospectively analyzed. According to the differences in surgical methods, patients undergoing laparoscopic hepatectomy were included in the laparoscopic group (n = 33), and patients undergoing percutaneous transhepatic choledochoscopy were included in the percutaneous transhepatic group (n = 32). The differences in perioperative indicators, inflammatory factors, postoperative complications, and one-year follow-up recurrence rates between the two groups were compared. RESULTS: Compared with percutaneous transhepatic group, laparoscopic group had significantly shorter operation time and hospitalization time (p < 0.05), and significantly higher blood loss (p < 0.05). After the operation, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the laparoscopic and percutaneous transhepatic groups were significantly lower than those in the same group before the operation (p < 0.05). CRP, TNF-α, and IL-6 in the laparoscopic group were significantly lower than in the percutaneous transhepatic group (p < 0.05). There was no significant difference in the incidence of postoperative complications and the recurrence rate of one-year follow-up between the laparoscopic group and the percutaneous transhepatic puncture group (p > 0.05). CONCLUSION: Laparoscopic hepatectomy and percutaneous transhepatic choledochoscopy are both practical and safe, and the appropriate surgical scheme should be selected according to the patient's specific condition.

Immunogenicity of COVID-19 vaccines in chronic liver disease patients and liver transplant recipients: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Chronic liver disease (CLD) patients and liver transplant (LT) recipients have an increased risk of morbidity and mortality from coronavirus disease 2019 (COVID-19). The immunogenicity of COVID-19 vaccines in CLD patients and LT recipients is poorly understood. The present study aimed to evaluate the immunogenicity of COVID-19 vaccines in CLD patients and LT recipients. METHODS: We searched electronic databases for eligible studies. Two reviewers independently conducted the literature search, extracted the data and assessed the risk of bias of included studies. The rates of detectable immune response were pooled from single-arm studies. For comparative studies, we compared the rates of detectable immune response between patients and healthy controls. The meta-analysis was conducted using the Stata software with a random-effects model. RESULTS: In total, 19 observational studies involving 4191 participants met the inclusion criteria. The pooled rates of detectable humoral immune response after two doses of COVID-19 vaccination in CLD patients and LT recipients were 95% (95% confidence interval [CI] = 88%-99%) and 66% (95% CI = 57%-74%) respectively. After two doses of vaccination, the humoral immune response rate was similar in CLD patients and healthy controls (risk ratio [RR] = 0.96; 95% CI = 0.90-1.02; p = .14). In contrast, LT recipients had a lower humoral immune response rate after two doses of vaccination than healthy controls (RR = 0.68; 95% CI = 0.59-0.77; p < .01). CONCLUSIONS: Our meta-analysis demonstrated that COVID-19 vaccination induced strong humoral immune responses in CLD patients but poor humoral immune responses in LT recipients.

Application of VCSEL in Bio-Sensing Atomic Magnetometers.

Recent years have seen rapid development of chip-scale atomic devices due to their great potential in the field of biomedical imaging, namely chip-scale atomic magnetometers that enable high resolution magnetocardiography (MCG) and magnetoencephalography (MEG). For atomic devices of this kind, vertical cavity surface emitting lasers (VCSELs) have become the most crucial components as integrated pumping sources, which are attracting growing interest. In this paper, the application of VCSELs in chip-scale atomic devices are reviewed, where VCSELs are integrated in various atomic bio-sensing devices with different operating environments. Secondly, the mode and polarization control of VCSELs in the specific applications are reviewed with their pros and cons discussed. In addition, various packaging of VCSEL based on different atomic devices in pursuit of miniaturization and precision measurement are reviewed and discussed. Finally, the VCSEL-based chip-scale atomic magnetometers utilized for cardiac and brain magnetometry are reviewed in detail. Nowadays, biosensors with chip integration, low power consumption, and high sensitivity are undergoing rapid industrialization, due to the growing market of medical instrumentation and portable health monitoring. It is promising that VCSEL-integrated chip-scale atomic biosensors as featured applications of this kind may experience extensive development in the near future.

Metastatic malignant melanoma from anorectum presenting as an isolated breast tumor: A case report and literature review.

RATIONALE: Anorectal malignant melanoma regularly exhibits a biological aggressive behavior which is metastasizing to lung, bone, brain or other organs and tissues early in the course of the disease. Compared with melanoma in the other parts of the body, anorectal malignant melanoma is relatively rare. Metastatic to the breast tissue from anorectal malignant melanoma or from other extra-mammary tumors are very rare. PATIENT CONCERNS: We report the case of a 65-year-old female who suffering from anorectal malignant melanoma and implemented complete surgical resection. Two years later, a space-occupying lesion in the outer upper quadrant of the right breast was observed on a chest CT. DIAGNOSIS: The right breast was excised, and breast metastasis of anorectal malignant melanoma was histologically confirmed. INTERVENTIONS: Radical mastectomy of the right breast was performed, and no lymph nodes or other metastases were observed. OUTCOMES: The patient's operative course was uneventful. The patient completely recovered and transfers to the oncology department for further treatment. LESSON: The patient presented with an isolated breast tumor. Duo to Malignant melanoma could mimic many kind of poorly differentiated tumors, it is difficult to diagnose accurately, especially when it appears as an isolated mammary tumor. Because of the treatment measures and prognosis between malignant melanoma and breast cancer are entirely different.

The predictive value of systemic immune inflammation index for postoperative survival of gallbladder carcinoma patients.

BACKGROUND: Growing evidence indicates that systemic immune inflammation index (SII) can predict the prognosis of various solid tumors. The objective of this study aimed to investigate the efficacy of SII in predicting the prognosis of gallbladder carcinoma (GBC) patients after radical surgery. METHODS: A consecutive series of 93 patients with GBC who underwent radical resection were enrolled in the retrospective study. The cutoff value for the SII was calculated using the time-dependent receiver operating characteristic (ROC) curve analysis by overall survival (OS) prediction. The associations between the SII and the clinicopathologic characteristics were analyzed using Pearson's χ2 test and Fisher's exact test. Survival curves were calculated using the Kaplan-Meier method. Univariate analysis was performed to evaluate the prognostic relevance of preoperative parameters. The multivariate Cox regression proportional hazard model was used to assess variables significant on univariate analysis. RESULTS: The Kaplan-Meier survival analysis and the multivariate analysis of patients with GBC who received radical resection showed SII independently predicted OS. The univariate analysis showed that the TNM stage, SII, CA19-9, ALP, prealbumin, NLR, MLR, lymph node metastasis, and histopathological type were all associated with overall survival. In time-dependent ROC analysis, the area of the SII-CA19-9 under the ROC curve (AUC) was higher than that of the preoperative SII or CA19-9 levels for the prediction of OS. CONCLUSION: Our results demonstrate that high SII was a predictor of poor long-term outcomes among patients with GBC undergoing curative surgery. SII-CA19-9 classification may be more effective in predicting the postoperative prognosis of GBC patients.

Spontaneous internal hemorrhage of a giant hepatic hemangioma with infection: a case report and literature review.

Spontaneous internal hemorrhage from a hepatic hemangioma is rare. This case describes a 59-year-old woman who was hospitalized with recurrent cough and fever for 6 months. The doctor thought that she had pneumonia, but other infectious diseases could not be ruled out. Therefore, related tests were performed and strong antibiotics were used, but the symptom of fever was persistent and recurred. Enhanced computed tomography (CT) findings showed a right hepatic giant hemangioma with hemorrhage, while tuberculosis, liver abscess, and immune disease were excluded by the physician. Because the patient's fever was associated with a large hepatic hemangioma, the patient was transferred to surgery. During treatment, the amount of bleeding increased, so she underwent a right hepatic hemangioma resection in the emergency department. Her postoperative fever symptoms subsequently resolved. Pathological examination confirmed hemorrhagic necrosis with infection in hepatic hemangioma. Follow-up showed that the patient was afebrile.

Bronchogenic cyst of the stomach: A case report and literature review.

Bronchogenic cyst (BC) is a rare congenital disease with pre-embryonic intestinal malformation. BC of the stomach is rare. The present study reported on the case of a 68-year-old male who presented with a spleen and stomach space mass detected incidentally upon a routine health examination. The patient underwent laparotomy. Postoperative histopathological diagnosis confirmed BC of the stomach. Postoperative recovery was smooth and the patient is currently under follow-up. A literature review suggested that BC is a rare disease and the location of the stomach is very rare. Indications of surgical intervention remain controversial for asymptomatic cases. Owing to no specific clinical or radiologic features to define the disease profile for diagnosis, surgery may be a good choice for both diagnosis and therapy if the patient's condition permits.

[Protective effect of serine methyltransferase against hepatic ischemia-reperfusion injury in mice].

OBJECTIVE: To investigate the protective effect of serine hydroxymethyl transferase 2 (SHMT2) against hepatic ischemia-reperfusion injury in mice. METHODS: Sixty C57BL/6 mice were divided equally into sham-operated group, saline adeno-associated virus group (AVV-GFP), and adeno-associated virus silencing group (AAV-SHMT2). The adeno-associated virus and normal saline were injected into the tail vein of the mice 2 weeks before establishment of a 70% ischemia-reperfusion model in the liver. qPCR, Western blotting, immunofluorescence and immunohistochemistry were used to detect the changes of AST/ALT concentration, SHMT2, JNK, NF-κB, caspase-3 and downstream inflammatory factors in the mice, and HE staining was used to observe the pathological damage of the liver tissue in each group; the cell apoptosis in the liver was detected using TUNEL assay. RESULTS: The expression of SHMT2 increased with time after hepatic ischemia-reperfusion and reached the highest level at 24 h (the relative expression was 1.5, P < 0.05). At 24 h after hepatic ischemia-reperfusion, the levels of AST/ALT in AAV-SHMT2 group (588/416 U/L) were significantly higher than those in the control group (416/345 U/L) and the empty vector group (387/321 U/L) (P < 0.05). Compared with those in the control group and the empty vector group, the level of SHMT2 was significantly decreased in AAV-SHMT2 group (with a relative expression of 0.24, P < 0.05), the levels of p-JNK and p-p65 were significantly increased (relative expression of 0.80 and 0.97, respectively, P < 0.05), and the levels TNF-α and IL-1ß were consistently elevated (relative expression levels of 1.6 and 1.2, respectively, P < 0.05). No significant differences were found in these parameters between the empty vector group and the control group (P>0.05). CONCLUSIONS: SHMT2 may alleviate liver cell apoptosis in mice with hepatic ischemia-reperfusion injury by inhibiting the activation of JNK pathway and excessive activation of NF-κB pathway to reduce hepatic damage.

Predictive value of CONUT score combined with serum CA199 levels in postoperative survival of patients with pancreatic ductal adenocarcinoma: a retrospective study.

BACKGROUND: The preoperative controlling nutritional status (CONUT) score and serum carbohydrate antigen 199 (CA199) levels are individually correlated with the prognosis of pancreatic ductal adenocarcinoma (PDAC). The objective of this study aimed to investigate the efficacy of CONUT score and CA199 (CONUT-CA199) combination in predicting the prognosis of PDAC patients undergoing radical surgery. METHODS: We retrospectively analyzed the preoperative CONUT scores and serum CA199 levels of 294 patients with PDAC who underwent radical resection at the Affiliated Hospital of Southwest Medical University between March 2012 and July 2019. Patients were divided into four groups on the basis of their preoperative CONUT scores and serum CA199 levels: CONUTlow/CA199low (1), CONUTlow/CA199high (2), CONUThigh/CA199low (3) and CONUThigh/CA199high (4). The prognostic effects were compared among the groups. RESULTS: CONUThigh was more frequent in patients with positive peripancreatic infiltration and Clavien-Dindo classification of ≥IIIa (P < 0.001). Kaplan-Meier analysis revealed obvious difference in overall survival (OS) and recurrence-free survival (RFS) among patients with PDAC having CONUT-CA199 scores of 1, 2, 3 and 4 (P < 0.001). Peripancreatic infiltration, lymph node metastasis, pTNM stage, CONUT score, serum CA199 levels and CONUT-CA199 classification were found to be the independent prognostic factors for OS and RFS in multivariate analyses. In time-dependent receiver operating characteristic (ROC) analyses, the area of the CONUT-CA199 score under the ROC curve (AUC) was higher than that of the preoperative CONUT score or serum CA199 levels for the prediction of OS and RFS. CONCLUSION: CONUT-CA199 classification may be more effective in predicting the postoperative prognosis of PDAC patients.

Hic-5 deficiency attenuates hepatic ischemia reperfusion injury through TLR4/NF-κB signaling pathways.

AIM: To explore the role and mechanism of Hydrogen peroxide-inducible clone-5 (Hic-5) in hepatic ischemia reperfusion injury. METHODS: Hic-5 KO and WT mice were used to establish the liver ischemia reperfusion model (HI/R). Primary hepatocytes were isolated to establish hypoxic reoxygenation model (H/R). AST and ALT were measured by automatic biochemical analyzer. Liver tissue sections were stained with HE and Tunnel. RNA and proteins were extracted from liver tissues, and expressions of Il-6, Il-10, CCL-2, CXCL-10, P65, Caspase-3, TLR4 and FADD were detected at gene and protein levels. Liver cell apoptosis was detected by flow cytometry and immunofluorescence. Primary hepatocytes were stimulated by LPS to establish a model of hepatocyte apoptosis, and cell inflammation and apoptosis-related proteins were detected. RESULTS: After HI/R, ALT and AST in serum were up-regulated, some hepatocyte apoptosis were observed in pathological sections. Hic-5 expression was increased in WT mice after HI/R, and liver damage were severer than KO mice. The expression of IL-6, CCL-2 and CXCL-10 in the liver of KO mice was low, and the expression of IL-10 was high. Further studies showed that KO mice showed lower expression of P65, Caspase3 and TLR4. In H/R model, hepatocytes also showed the same trend. Finally, after LPS stimulation, the results showed that the inflammation and apoptosis induced by LPS were significantly reduced in Hic-5 knocked hepatocytes. CONCLUSION: Hic-5 was found to promote inflammation through NF-kb signaling pathway and apoptosis through TLR4-FADD signaling pathway in mice with HI/R, thus aggravating liver injury in mice.

Hic-5 in pancreatic stellate cells affects proliferation, apoptosis, migration, invasion of pancreatic cancer cells and postoperative survival time of pancreatic cancer.

Pancreatic cancer is one of the most severe types of tumors, with a 5-year survival rate of less than 7%. The prognosis and treatment of pancreatic cancer are largely limited by the extent of tumor invasion and the presence of lymph node and distant metastases. Therefore, exploring the biological behavior of pancreatic cancer cells (PCCs) is extremely important for the understanding, diagnosis, and treatment of pancreatic cancer. Current studies have shown that pancreatic stellate cells (PSCs) regulate the biological behavior of PCCs, such as their proliferation, apoptosis, invasion, and migration, by remodeling the extracellular matrix. Though Hic-5 is an important gene in PSCs, no study has investigated the regulation of PCCs by Hic-5. Here, we demonstrate that Hic-5 expression is upregulated in pancreatic cancer and that siRNA transfection can effectively inhibit Hic-5 expression. Compared to the control group, Hic-5 inhibition significantly reduced proliferation, increased apoptosis, and reduced invasion and migration of PCCs. Moreover, the inhibition of Hic-5 expression simultaneously reduced matrix metalloproteinase-9 (MMP-9) expression. Statistical analysis revealed that Hic-5 expression was higher among the pancreatic cancer group than among the normal group and was negatively correlated with postoperative survival time among patients with pancreatic cancer. These results have important clinical significance for further exploring the molecular mechanism involved in Hic-5-mediated invasion and metastasis of pancreatic cancer and ameliorating the prognosis of patients with pancreatic cancer.

Controlling Nutritional Status (CONUT) Score as a New Indicator of Prognosis in Patients With Hilar Cholangiocarcinoma Is Superior to NLR and PNI: A Single-Center Retrospective Study.

BACKGROUND: Currently, many nutritional indicators, including controlling nutritional status score (CONUT), can be used to assess a patient's nutritional status and have been reported as reliable predictors of multiple malignancies. However, the value of CONUT score in predicting postoperative outcomes in patients with hilar cholangiocarcinoma has not been explored. In this study, its predictive value will be discussed and compared with the known predictors the neutrophil lymphocyte ratio (NLR) and prognostic nutritional index (PNI). METHODS: Preoperative CONUT scores, PNI and NLR levels of 94 Hilar cholangiocarcinoma (HCCA) patients who underwent radical-intent resection of hepatobiliary surgery in our hospital from March 2010 to April 2019 were retrospectively collected and analyzed. They were grouped according to their optimal cutoff value and the prognostic effects of patients in each group were compared respectively. RESULTS: CONUThigh was more frequent in patients with Clavien-Dindo classification of ≥IIIa (P = 0.008) and Bile leakage presence (P = 0.011). Kaplan-Meier curves analyzing the relationship between CONUT, PNI, and NLR values and HCCA patient survival (including total survival (OS) and recurrence-free survival (RFS) showed significant differences between groups (P <0.001). Meanwhile, multi-factor analysis found that Degree of cure, PNI, NLR, and preoperative CONUT score were independent prognostic factors for OS and RFS. The predictive power of CONUT score was higher than that of NLR and PNI based on time-dependent receiver operating Characteristic (ROC) analysis and the net reclassification index (NRI) and integrated discriminatory index (IDI) values (P < 0.05). CONCLUSION: CONUT score may be of some clinical reference value in evaluating postoperative prognosis of HCCA patients.

Hic-5 deficiency protects cerulein-induced chronic pancreatitis via down-regulation of the NF-κB (p65)/IL-6 signalling pathway.

Chronic pancreatitis (CP), characterized by pancreatic fibrosis, is a recurrent, progressive and irreversible disease. Activation of the pancreatic stellate cells (PSCs) is considered a core event in pancreatic fibrosis. In this study, we investigated the role of hydrogen peroxide-inducible clone-5 (Hic-5) in CP. Analysis of the human pancreatic tissue samples revealed that Hic-5 was overexpressed in patients with CP and was extremely low in healthy pancreas. Hic-5 was significant up-regulated in the activated primary PSCs independently from transforming growth factor beta stimulation. CP induced by cerulein injection was ameliorated in Hic-5 knockout (KO) mice, as shown by staining of tissue level. Simultaneously, the activation ability of the primary PSCs from Hic-5 KO mice was significantly attenuated. We also found that the Hic-5 up-regulation by cerulein activated the NF-κB (p65)/IL-6 signalling pathway and regulated the downstream extracellular matrix (ECM) genes such as α-SMA and Col1a1. Therefore, we determined whether suppressing NF-κB/p65 alleviated CP by treating mice with the NF-κB/p65 inhibitor triptolide in the cerulein-induced CP model and found that pancreatic fibrosis was alleviated by NF-κB/p65 inhibition. These findings provide evidence for Hic-5 as a therapeutic target that plays a crucial role in regulating PSCs activation and pancreatic fibrosis.

Aloin Preconditioning Attenuates Hepatic Ischemia/Reperfusion Injury via Inhibiting TLR4/MyD88/NF-κB Signal Pathway In Vivo and In Vitro.

BACKGROUND: Aloin exerts considerable protective effects in various disease models, and its effect on hepatic ischemia-reperfusion (HIR) injury remains unknown. This research is aimed at conducting an in-depth investigation of the antioxidant, anti-inflammatory, and antiapoptosis effects of aloin in HIR injury and explain the underlying molecular mechanisms. METHODS: In vivo, different concentrations of aloin were intraperitoneally injected 1 h before the establishment of the HIR model in male mice. The hepatic function, pathological status, oxidative stress, and inflammatory and apoptosis markers were measured. In vitro, aloin (AL, C21H22O9) or lipopolysaccharide (LPS) was added to a culture of mouse primary hepatocytes before it underwent hypoxia/reoxygenation (H/R), and the apoptosis in the mouse primary hepatocytes was analyzed. RESULTS: We found that 20 mg/kg was the optimum concentration of aloin for mitigating I/R-induced liver tissue damage, characterized by decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Aloin pretreatment substantially suppressed the generation of hepatic malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and IL-6 and enhanced the hepatic superoxide dismutase (SOD) activities as well as glutathione (GSH) and IL-10 levels in the liver tissue of I/R mice; this indicated that aloin ameliorated I/R-induced liver damage by reducing the oxidative stress and inflammatory response. Moreover, aloin inhibited hepatocyte apoptosis and inflammatory response that was caused by the upregulated expression of Bcl-2, the downregulated expression of cleaved caspase3(C-caspase3), Bax, Toll-like receptor 4 (TLR4), FADD, MyD88, TRAF6, phosphorylated IKKα/ß (p-IKKα/ß), and phosphorylated nuclear factor κB p65 (p-NF-κB p65).

SPOP inhibits mice pancreatic stellate cell activation by promoting FADD degradation in cerulein-induced chronic pancreatitis.

Pancreatic stellate cells (PSCs) have been recognized as key mediators of pancreatic fibrosis, a characteristic feature of chronic pancreatitis (CP). As a cullin-based E3 ubiquitin ligase, speckle-type POZ protein (SPOP) has been identified to participate in tumorigenesis and organ development. However, its biological role in CP remains unknown. Therefore, this study sought to investigate the changed expression of SPOP in CP and to examine the effect on mice PSCs activation of SPOP. We found that SPOP was downregulated in the pancreatic tissues of cerulein-induced CP mice. siRNA-mediated knockdown of SPOP led to significant promotion in primary PSCs activity by activating the nuclear factor-kappaB (NF-κB)/interleukin-6 (IL-6) signaling pathway. In addition, we examined the effects of Fas-associated death domain (FADD), a proven SPOP substrate that activates NF-κB, on the regulation of PSCs activation. We found that FADD was downregulated by SPOP via interaction-mediated degradation, and was upregulated during PSCs activation. The promotion of PSCs activation in knocking down SPOP with siSPOP-1 were counteracted by knocking down FADD. The results suggest that the SPOP-induced inhibition of PSCs activation partially depended on FADD. These results highlight the importance of SPOP in CP and provide a potential target for therapeutic intervention.