Prognostic value of a nomogram model for postoperative liver metastasis of colon cancer.

BACKGROUND: Colon cancer is one of the most common malignant tumors of the digestive system. Liver metastasis after colon cancer surgery is the primary cause of death in patients with colon cancer. AIM: To construct a novel nomogram model including various factors to predict liver metastasis after colon cancer surgery. METHODS: We retrospectively analyzed 242 patients with colon cancer who were admitted and underwent radical resection for colon cancer in Zhejiang Provincial People's Hospital from December 2019 to December 2022. Patients were divided into liver metastasis and non-liver metastasis groups. Sex, age, and other general and clinicopathological data (preoperative blood routine and biochemical test indexes) were compared. The risk factors for liver metastasis were analyzed using single-factor and multifactorial logistic regression. A predictive model was then constructed and evaluated for efficacy. RESULTS: Systemic inflammatory index (SII), C-reactive protein/albumin ratio (CAR), red blood cell distribution width (RDW), alanine aminotransferase, preoperative carcinoembryonic antigen level, and lymphatic metastasis were different between groups (P < 0.05). SII, CAR, and RDW were risk factors for liver metastasis after colon cancer surgery (P < 0.05). The area under the curve was 0.93 for the column-line diagram prediction model constructed based on these risk factors to distinguish whether liver metastasis occurred postoperatively. The actual curve of the column-line diagram predicting the risk of postoperative liver metastasis was close to the ideal curve, with good agreement. The prediction model curves in the decision curve analysis showed higher net benefits for a larger threshold range than those in extreme cases, indicating that the model is safer. CONCLUSION: Liver metastases after colorectal cancer surgery could be well predicted by a nomogram based on the SII, CAR, and RDW.

Identification and validation of palmitoylation metabolism-related signature for liver hepatocellular carcinoma.

BACKGROUND: Protein S-palmitoylation is a reversible posttranslational modification widely involved in tumor progression. Nevertheless, the function of palmitoylation metabolism in prognosis and tumor microenvironment characteristics in liver hepatocellular carcinoma (LIHC) patients is not fully understood. METHODS: mRNA and clinical data of LIHC patients were obtained from the TCGA and ICGC databases. Consensus clustering was used to construct palmitoylation metabolism-related clusters. Univariate Cox and Lasso regression analyses were employed to establish a palmitoylation metabolism-related signature (PMS). ssGSEA was applied to evaluate the immune cell score in each LIHC sample. Functional enrichments were accessed through GO, KEGG and GSVA. Drug sensitivity data were downloaded from the GDSC database. RESULTS: Three palmitoylation metabolism-related clusters with different prognostic and immune infiltration characteristics were constructed in LIHC. We identified PMS with distinct survival, clinical, and tumor immune microenvironment characteristics. The high PMS group had a poorer prognosis, higher infiltration of immunosuppressive cells and higher expression of immune checkpoints. ZDHHC20 exerted a tumor-promoting role in LIHC and was significantly associated with immunosuppressive cells and immunosuppressive checkpoints. Additionally, in HepG-2 and SMCC-7721 cells, si-ZDHHC20 boosted apoptosis but decreased proliferation and migration when compared to si-NC. CONCLUSION: Our research revealed that PMS may accurately predict the prognosis and immune characteristics of LIHC patients. ZDHHC20 has significant clinical and immune relevance in LIHC and may contribute to the formulation of new targets for LIHC immunotherapy.

Application of sintilimab combined with anlotinib hydrochloride in the clinical treatment of microsatellite stable colorectal cancer.

BACKGROUND: Microsatellite stable (MSS) colorectal cancer (CRC) is a common type of tumor with limited treatment options. Sintilimab and anlotinib hydrochloride are two extensively studied anticancer drugs. AIM: To probe the clinical value of combining sintilimab with anlotinib hydrochloride in MSS CRC treatment. METHODS: During the period spanning from April 2019 to April 2022, Zhejiang Provincial People's Hospital accommodated a cohort of 92 patients diagnosed with MSS CRC who were classified into two distinct groups in our study, the observation group and the control group. The control group was administered anlotinib hydrochloride as their designated therapy, whereas the observation group received the additional treatment of sintilimab in conjunction with the therapy assigned to the control group. The administration of treatment occurred in cycles consisting of a duration of 3 wk, and the evaluation of effectiveness took place subsequent to the completion of two consecutive cycles of treatment within both groups. A comparative analysis between the two groups was conducted to assess the short-term efficacy and ascertain the incidence of adverse events transpiring throughout the duration of the treatment period. Changes in the levels of carcinoembryonic antigen, carbohydrate antigen 199 (CA199), CA125, and T cell subsets (CD4+, CD8+, CD4+/CD8+) as well as the assessment of the quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 were compared between the two groups prior to and subsequent to therapy. Finally, a 1-year follow-up was conducted for both groups of patients, and the survival status was recorded and analyzed. RESULTS: The short-term effectiveness displayed by the observation group surpassed that exhibited by the control group, with a statistically significant discrepancy (76.09% vs 50.00%), reaching a significance level denoted as P < 0.05. Following the administration of treatment, the observation group manifested a considerable reduction in numerous serum indicators, which were found to be lower than the corresponding pretreatment levels within the same group as well as the post-treatment levels observed in the control group (P < 0.05). Post-treatment, the T lymphocyte subset levels within the observation group demonstrated a remarkable amelioration, surpassing the corresponding pre-treatment levels observed within the same group as well as the post-treatment levels observed in the control group (P < 0.05). Subsequent to the therapeutic intervention, the observation group showcased a notable amelioration in the scores associated with multiple dimensions of life quality. These scores outperformed the pretreatment scores within the same group as well as the post-treatment scores observed in the control group (P < 0.05). The safety levels of drug use in the two group were comparable (19.57% vs 13.04%), and no distinct difference was observed upon comparison (P > 0.05). After the completion of treatment, both groups of patients underwent a 1-year follow-up outside the hospital. Throughout this period, 1 patient within the observation group and 2 patients within the control group became untraceable and were lost to follow-up. During the follow-up period of the observation group, 12 patients died, resulting in a survival rate of 73.33% (33/45), while in the control group, 21 patients died, resulting in a survival rate of 52.27% (23/44). The implementation of Kaplan-Meier survival analysis revealed a conspicuous contrast in survival rates exhibited by the two groups (log-rank = 4.710, P = 0.030). CONCLUSION: The combination of sintilimab and anlotinib hydrochloride demonstrated favorable efficacy in the treatment of MSS CRC patients, leading to improvements in patient immunity and prognosis. Additionally, it exerted inhibitory effects on the expression of carcinoembryonic antigen, CA199, and CA125.

Efficacy and safety analysis of transarterial chemoembolization and transarterial radioembolization in advanced hepatocellular carcinoma descending hepatectomy.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, which is seriously threatening the lives of patients. Due to the rapid development of the disease, patients were in the middle and advanced stages at the time of diagnosis and missed the best time for treatment. With the development of minimally invasive medicine, interventional therapy for advanced HCC has achieved promising results. Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are currently recognized as effective treatments. This study aimed to investigate the clinical value and safety of TACE alone and combined with TACE in the treatment of progression in patients with advanced HCC and to find a breakthrough for the early diagnosis and treatment of patients with advanced HCC. AIM: To investigate the efficacy and safety of hepatic TACE and TARE in advanced descending hepatectomy. METHODS: In this study, 218 patients with advanced HCC who were treated in the Zhejiang Provincial People's Hospital from May 2016 to May 2021 were collected. Of the patients, 119 served as the control group and received hepatic TACE, 99 served as the observation group and were treated with hepatic TACE combined with TARE. The patients in two groups were compared in terms of lesion inactivation, tumor nodule size, lipiodol deposition, serum alpha-fetoprotein (AFP) level in different periods, postoperative complications, 1-year survival rate, and clinical symptoms such as liver pain, fatigue, and abdominal distension, and adverse reactions such as nausea and vomiting. RESULTS: The observation group and the control group had good efficacy in treatment efficiency, reduction of tumor nodules, reduction of postoperative AFP value, reduction of postoperative complications, and relief of clinical symptoms. In addition, compared with the control group, the treatment efficiency, reduction of tumor nodules, reduction of AFP value, reduction of postoperative complications, and relief of clinical symptoms in the observation group were better than those in the TACE group alone. Patients in the TACE + TARE group had a higher 1-year survival rate after surgery, lipiodol deposition was significantly increased and the extent of tumor necrosis was expanded. The overall incidence of adverse reactions in the TACE + TARE group was lower than that in the TACE group, and the difference had statistical significance (P < 0.05). CONCLUSION: Compared with TACE alone, TACE combined with TARE is more effective in the treatment of patients with advanced HCC. It also improves postoperative survival rate, reduces adverse effects, and has a better safety profile.

Clinical efficacy comparison of sclerosing embolization with 3% polidocanol and the microsurgical subinguinal varicocelectomy in primary varicocele patients.

Varicocele is a more common male genitourinary system disease with sperm quality dysfunction or discomfort. This study was aimed to compare the clinical efficacy of sclerosing embolization with 3% polidocanol and the microsurgical subinguinal varicocelectomy in treating primary varicocele. Total of 59 patients with primary varicocele receiving a 3-month postoperative follow-up were included to analyse their biochemical parameters and clinical outcomes, including the operative time, hospitalization time, postoperative recurrence rates, and complication rate. Nineteen patients were treated with sclerosing embolization with 3% polidocanol (SE group), while 40 patients were treated with microsurgical subinguinal varicocelectomy (MSV group). For the SE group, 17 patients were treated on the left side, and two patients have treated on both without recurrences and complications during the follow-up period. For the MSV group, three patients were treated bilaterally, and 36 patients were treated separately on the left side with a total 5% recurrence rate and 10% complication rate. The duration of surgery and the hospitalization time of the SE group (46.2 ± 9.79 min and 2.53 ± 0.90 days, respectively) are significantly lower than MSV group (100.5 ± 13.76 min and 3.6 ± 1.58 days, respectively), p < 0.05. The total sperm count at 3 months was significantly higher in the SE group than in the MSV group (p < 0.05). In summary, sclerosing embolization is more effective for varicocele in improving sperm quality, shortening recovery time, and reducing recurrence rates and complications.

An Autophagy-Related Gene-Based Prognostic Risk Signature for Hepatocellular Carcinoma: Construction and Validation.

BACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer. Treatment is dramatically difficult due to its high complexity and poor prognosis. Due to the disclosed dual functions of autophagy in cancer development, understanding autophagy-related genes devotes into novel biomarkers for HCC. METHODS: Differential expression of genes in normal and tumor groups was analyzed to acquire autophagy-related genes in HCC. These genes were subjected to GO and KEGG pathway analyses. Genes were then screened by univariate regression analysis. The screened genes were subjected to multivariate Cox regression analysis to build a prognostic model. The model was validated by the ICGC validation set. RESULTS: To sum up, 42 differential genes relevant to autophagy were screened by differential expression analysis. Enrichment analysis showed that they were mainly enriched in pathways including regulation of autophagy and cell apoptosis. Genes were screened by univariate analysis and multivariate Cox regression analysis to build a prognostic model. The model constituted 6 feature genes: EIF2S1, BIRC5, SQSTM1, ATG7, HDAC1, and FKBP1A. Validation confirmed the accuracy and independence of this model in predicting the HCC patient's prognosis. CONCLUSION: A total of 6 feature genes were identified to build a prognostic risk model. This model is conducive to investigating interplay between autophagy-related genes and HCC prognosis.

Scoring Model to Predict Functional Outcome in Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

Background: Patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH), defined as World Federation of Neurosurgical Societies (WFNS) grades IV-V have high rates of disability and mortality. The objective of this study was to accurately prognosticate the outcomes of patients with poor-grade aSAH by developing a new scoring model. Methods: A total of 147 poor-grade aSAH patients in our center were enrolled. Risk variables identified by multivariate logistic regression analysis were used to devise a scoring model (total score, 0-9 points). The scores were estimated on the basis of ß coefficients. A cohort of 68 patients from another institute was used to validate the model. Results: Multivariate logistic regression analysis revealed that modified Fisher grade >2 [odds ratio [OR], 2.972; P = 0.034], age ≥65 years (OR, 3.534; P = 0.006), conservative treatment (OR, 5.078; P = 0.019), WFNS grade V (OR, 2.638; P = 0.029), delayed cerebral ischemia (OR, 3.170; P = 0.016), shunt-dependent hydrocephalus (OR, 3.202; P = 0.032), and cerebral herniation (OR, 7.337; P < 0.001) were significant predictors for poor prognosis [modified Rankin Scale [mRS] ≥3]. A scoring system was constructed by the integration of these factors and divided the poor-grade aSAH patients into three categories: low risk (0-1 points), intermediate risk (2-3 points), and high risk (4-9 points), with predicted risks of poor prognosis of 11, 52, and 87%, respectively (P < 0.001). The area under the curve in the derivation cohort was 0.844 (95% CI, 0.778-0.909). The AUC in the validation cohort was 0.831 (95% CI, 0.732-0.929). Conclusions: The new scoring model can improve prognostication and help decision-making for subsequent complementary treatment in patients with aSAH.

PTP1B inhibitor alleviates deleterious microglial activation and neuronal injury after ischemic stroke by modulating the ER stress-autophagy axis via PERK signaling in microglia.

Cerebral ischemia/reperfusion (IR) after ischemic stroke causes deleterious microglial activation. Protein tyrosine phosphatase 1B (PTP1B) exacerbates neuroinflammation, yet the effect of the inhibition on microglial activation and cerebral IR injury is unknown. A cerebral IR rat model was induced by middle cerebral artery occlusion (MCAO) and reperfusion. The PTP1B inhibitor, sc-222227, was administered intracerebroventricularly. Neurologic deficits, infarct volume, and brain water content were examined. An in vitro oxygen glucose deprivation/reoxygenation (OGD/R) model was established in primary microglia and BV-2 cells. Microglial activation/polarization, endoplasmic reticulum (ER) stress, autophagy, and apoptosis were detected using western blot, immunohistology, ELISA, and real-time PCR. Protein interaction was assessed by a proximity ligation assay. The results showed a significant increase in microglial PTP1B expression after IR injury. Sc-222227 attenuated IR-induced microglial activation, ER stress, and autophagy and promoted M2 polarization. Upon OGD/R, sc-222227 mitigated microglial activation by inhibiting ER stress-dependent autophagy, the effect of which was abolished by PERK activation, and PERK inhibition attenuated microglial activation. The PTP1B-phosphorylated PERK protein interaction was significantly increased after OGD/R, but decreased upon sc-222227 treatment. Finally, sc-222227 mitigated neuronal damage and neurologic deficits after IR injury. Treatment targeting microglial PTP1B might be a potential therapeutic strategy for ischemic stroke treatment.

Serum Alkaline Phosphatase Level is Associated with Angiographic Vasospasm, Delayed Cerebral Ischemia-Caused Clinical Deterioration, and Functional Outcome After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Alkaline phosphatase (ALP) has been implicated to be associated with poor outcome in ischemic stroke patients, yet its role in aneurysmal subarachnoid hemorrhage (aSAH) patients is unknown. The current study aimed to investigate the on-admission and short-term variation trend of ALP levels in aSAH patients as well as its associations with vasospasm, delayed cerebral ischemia (DCI), and outcome after aSAH. METHODS: Between January 2014 and May 2018, all consecutive aSAH patients were prospectively enrolled. Blood samples from patients and 78 healthy individuals were obtained. Baseline information, clinical data, and radiologic data were collected, and serum ALP levels during hospitalization were measured. Patients were followed up for 6 months. RESULTS: One hundred and ninety-six aSAH patients were included. The serum ALP levels in aSAH patients were significantly higher compared to controls (71 vs. 61 U/L, p = 0.0002), yet did not differ significantly between patients with severe (WFNS 4-5) and mild clinical condition (72 vs. 63 U/L, p = 0.3362). However, ALP was significantly higher in patients with severe radiologic status (modified Fisher 3-4) compared to those with mild radiologic status (77 vs. 61.5 U/L, p = 0.0005). A significant correlation emerged between modified Fisher score and ALP level (r = 0.246, p = 0.001). Multivariable analysis found that higher ALP level was associated with angiographic vasospasm (OR 1.019, 95% CI 1.002-1.036, p = 0.026) and DCI-caused clinical deterioration (OR 1.019, 95% CI 1.001-1.037, p = 0.037), while higher WFNS score, modified Fisher score, and ALP level were independently associated with unfavorable outcome (serum ALP level, OR 1.083, 95% CI 1.041-1.127, p < 0.001). Trend analysis of ALP level based on 103 patients' data revealed a significant decrease in ALP level on post-admission day 7-9 (median; on-admission day vs. post-admission day 7-9, 72 vs. 60 U/L, p = 0.0012; post-admission day 3-5 vs. day 7-9, 70 vs. 60 U/L, p = 0.0052) and subsequent increase in ALP level on post-admission day 12-14 (median, 84 U/L, p < 0.0001). Higher ALP levels were observed in patients with unfavorable outcome on on-admission day, post-admission day 3-5, and 12-14 (median; unfavorable vs. favorable; on-admission day, 86 vs. 67 U/L, p = 0.0122; post-admission day 3-5, 80 vs. 64 U/L, p = 0.0044; post-admission day 7-9, 75 vs. 53.5 U/L, p < 0.0001) but not on post-admission day 12-14. CONCLUSIONS: Elevated serum ALP level is associated with vasospasm, DCI-caused clinical deterioration, and functional outcome after aSAH. Further studies are required to examine the potential role of serum ALP as an outcome predictor for aSAH patients.