Prediction of clinical prognosis and drug sensitivity in hepatocellular carcinoma through the combination of multiple cell death pathways.

Hepatocellular carcinoma (HCC) is the sixth most common malignant tumor, highlighting a significant need for reliable predictive models to assess clinical prognosis, disease progression, and drug sensitivity. Recent studies have highlighted the critical role of various programmed cell death pathways, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, entotic cell death, NETotic cell death, parthanatos, lysosome-dependent cell death, autophagy-dependent cell death, alkaliptosis, oxeiptosis, and disulfidptosis, in tumor development. Therefore, by investigating these pathways, we aimed to develop a predictive model for HCC prognosis and drug sensitivity. We analyzed transcriptome, single-cell transcriptome, genomic, and clinical information using data from the TCGA-LIHC, GSE14520, GSE45436, and GSE166635 datasets. Machine learning algorithms were used to establish a cell death index (CDI) with seven gene signatures, which was validated across three independent datasets, showing that high CDI correlates with poorer prognosis. Unsupervised clustering revealed three molecular subtypes of HCC with distinct biological processes. Furthermore, a nomogram integrating CDI and clinical information demonstrated good predictive performance. CDI was associated with immune checkpoint genes and tumor microenvironment components using single-cell transcriptome analysis. Drug sensitivity analysis indicated that patients with high CDI may be resistant to oxaliplatin and cisplatin but sensitive to axitinib and sorafenib. In summary, our model offers a precise prediction of clinical outcomes and drug sensitivity for patients with HCC, providing valuable insights for personalized treatment strategies.

Clinical, Microbiological, and Molecular Characterization of Candia (Starmera) stellimalicola, a Rare Fungal Pathogen Causing Human Infections.

Candia (Starmera) stellimalicola is a yeast species spread worldwide and recovered from varieties of ecological reservoirs, but human infections are rarely reported. In this study, we reported an intra-abdominal infection case caused by C. stellimalicola and described its microbiological and molecular characteristics. C. stellimalicola strains were isolated from ascites fluid of an 82-year-old male patient having diffuse peritonitis with fever and elevated WBC counts. Routine biochemical and MALDI-TOF MS methods failed to identify the pathogenic strains. Phylogenetic analysis of 18S, 26S and internal transcribed space (ITS) rDNA regions, as well as whole-genome sequence identified the strains as C. stellimalicola. Compared with other Starmera species, C. stellimalicola had unique physiological characteristics including thermal tolerance (able to grow at 42 °C), which may prompt its environmental adaptability and potential for opportunistic human infection. Fluconazole minimum inhibitory concentration (MIC) values of the strains identified in this case was 2 mg/L, and the patient had a favorable outcome after receiving fluconazole treatment. In comparison, the majority of C. stellimalicola strains previously documented had high MIC values (≥ 16 mg/L) to fluconazole. In conclusion, with the raise in human infections caused by rare fungal pathogens, molecular diagnostic remains the most efficient way for accurate species identification; and antifungal susceptibility testing is essential to guide proper patient management.

Online calculators for predicting the risk of anastomotic stricture after hepaticojejunostomy for bile duct injury after cholecystectomy: a multicenter retrospective study.

BACKGROUND: Anastomotic stricture is a common underlying cause of long-term morbidity after hepaticojejunostomy (HJ) for bile duct injury (BDI) following cholecystectomy. However, there are no methods for predicting stricture risk. This study was aimed at establishing two online calculators for predicting anastomotic stricture occurrence (ASO) and stricture-free survival (SFS) in this patient population. METHODS: The clinicopathological characteristics and follow-up information of patients who underwent HJ for BDI after cholecystectomy from a multi-institutional database were reviewed. Univariate and multivariate analyses of the risk factors of ASO and SFS were performed in the training cohort. Two nomogram-based online calculators were developed and validated by internal bootstrapping resamples ( n =1000) and an external cohort. RESULTS: Among 220 screened patients, 41 (18.64%) experienced anastomotic strictures after a median follow-up of 110.7 months. Using multivariate analysis, four variables, including previous repair, sepsis, HJ phase, and bile duct fistula, were identified as independent risk factors associated with both ASO and SFS. Two nomogram models and their corresponding online calculators were subsequently developed. In the training cohort, the novel calculators achieved concordance indices ( C -indices) of 0.841 and 0.763 in predicting ASO and SFS, respectively, much higher than those of the above variables. The predictive accuracy of the resulting models was also good in the internal ( C -indices: 0.867 and 0.821) and external ( C -indices: 0.852 and 0.823) validation cohorts. CONCLUSIONS: The two easy-to-use online calculators demonstrated optimal predictive performance for identifying patients at high risk for ASO and with dismal SFS. The estimation of individual risks will help guide decision-making and long-term personalized surveillance.

Molecular subtypes predict the preferential site of distant metastasis in advanced breast cancer: a nationwide retrospective study.

Objective: This study aimed to explore possible associations between molecular subtypes and site of distant metastasis in advanced breast cancer (ABC). Methods: 3577 ABC patients were selected from 21 hospitals of seven geographic regions in China from 2012-2014. A questionnaire was designed to collect medical information regarding demographic characteristics, risk factors, molecular subtype, recurrence/metastasis information, and disease-free survival (DFS). The cancers were classified into Luminal A, Luminal B, HER2-enriched and Triple Negative subtypes. Chi-square test and multivariate Cox proportional hazard models were performed to explore the associations between molecular subtypes and distant metastasis sites. Results: A total of 2393 cases with molecular subtypes information were finally examined. Patients with Luminal A (51.1%) and Luminal B (44.7%) were most prone to bone metastasis, whereas liver metastasis was more frequently observed in HER2-enriched ABC patients (29.1%).The cumulative recurrence and metastasis rates of ABC patients at 36 months of DFS were the most significant within molecular types, of which Triple Negative was the highest (82.7%), while that of Luminal A was the lowest (58.4%). In the adjusted Cox regression analysis, Luminal B, HER2-enriched and Triple Negative subtypes increased the risk of visceral metastasis by 23%, 46% and 87% respectively. In addition, Triple Negative patients had a higher probability of brain metastasis (HR 3.07, 95% CI: 1.04-9.07). Conclusion: Molecular subtypes can predict the preferential sites of distant metastasis, emphasizing that these associations were of great help in choices for surveillance, developing appropriate screening and cancer management strategies for follow-up and personalized therapy in ABC patients.

Age at initial diagnosis and prognosis of breast cancer: a nationwide multicenter retrospective study in China.

Background: Several studies have indicated possible associations between age and the prognosis of breast cancer (BC), but limited data are available from hospital-based multicenter studies in China. This study aimed to explore the associations between age at initial diagnosis of BC and the risk of recurrence or metastasis among Chinese women with newly diagnosed advanced breast cancer (ABC) and provide treatment decision support for BC patients of different ages to medical workers. Methods: The medical records of patients newly diagnosed with ABC were obtained from 21 hospitals in seven geographic regions in China from 2012 to 2014. Patients' general information, clinicopathological features at first diagnosis, treatment information, and prognosis were retrospectively collected based on the self-designed case report form (CRF). Cox proportional hazards regression models were used to determine hazard ratios (HR) and 95% confidence intervals (CI) for the associations between age groups and the risk of recurrence and metastasis. Results: A total of 1,852 cases were included in the final analysis. Age at initial diagnosis was shown to be significantly related to hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, molecular subtypes, and the number of lymph node metastasis (all P<0.05). Patients aged <35 years were more likely to have bone metastasis (45.6%). Patients aged ≥65 years had a lower percentage of receiving surgery (87.1%), adjuvant chemotherapy (61.3%), adjuvant radiotherapy (35.5%), and adjuvant endocrine therapy (30.6%) than the other groups (all P<0.05). Compared with patients aged <35 years, the risk of recurrence or metastasis in those aged 55-64 years was significantly higher (HRage 55-64 =1.24, 95% CI: 1.04-1.47), and the risk of bone metastasis and lung metastasis in those aged 35-44 years was lower (HRbone metastasis =0.74, 95% CI: 0.59-0.93; HRlung metastasis =0.70, 95% CI: 0.53-0.93). After adjusting for stage, grade, and molecular subtype, surgery, neoadjuvant chemotherapy, adjuvant chemotherapy, adjuvant radiotherapy, adjuvant endocrine therapy, and family history of BC, patients aged 35-44 years still had a significantly reduced risk of bone metastasis and lung metastasis by 31% and 52%, respectively (HRbone metastasis =0.69, 95% CI: 0.48-0.98; HRlung metastasis =0.48, 95% CI: 0.31-0.74). Conclusions: Age at initial diagnosis is related to the clinicopathological characteristics and treatment pattern. Although the risk of site-specific metastasis varies by age, age is not an independent factor influencing the risk of total recurrence and metastasis. In accordance with current clinical practice guidelines for BC, however, precise treatment shall be chosen personally for patients whose ages at initial diagnosis are different.

Water-Soluble Polysaccharides Extracted from Pueraria lobata Delay Aging of Caenorhabditis elegans under Heat Stress.

Pueraria lobata is a perennial legume, commonly used as a food source in China. The polysaccharides extracted from P. lobata have demonstrated various biological activities. However their anti-aging effects and the underline mechanisms are largely unknown. In this study, water-soluble polysaccharides (WSPS) from P. lobata were extracted and demonstrated antioxidant activity against DPPH radicals and hydroxyl radicals in vitro. Using nematode Caenorhabditis elegans as a model, we found that WSPS remarkably prolonged the survival, increased growth and locomotion under heat stress. To investigate the possible mechanism, the levels of reactive oxygen species (ROS) and lipid peroxidation product malondialdehyde (MDA) were determined. WSPS significantly decreased ROS and MDA levels which is consistent with increased activity of superoxide dismutase (SOD). Meanwhile, WSPS upregulated the expression of stress resistance genes sod-1, sod-5, hsf-1, hsp-12.6, hsp-16.2, skn-1 and gst-4. Together, these results suggest that the anti-aging activity of WSPS under heat stress was mediated most likely by activation of the target genes of heat-shock transcription factor (HSF)-1 and skinhead (SKN)-1, and thus inducing endogenous ROS scavenging response.

Successful Surgical Removal of a Huge Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Hepatectomy and transcatheter arterial chemoembolisation (TACE) are generally accepted methods for the treatment of huge HCCs, but the most appropriate treatment is still controversial. We report a 43-year woman with giant HCC, who successfully underwent surgery. The patient was admitted with persistent right upper abdominal pain and fever. Before operation, we assessed the residual liver function and reserve capacity of the patient, and excluded the relevant surgical contra-indications. The results showed that the patient could tolerate surgical treatment, so we performed HCC resection, and the patient was successfully treated. Individualised treatment should be carried out according to tumor factors, baseline liver function and patient's functional status, so as to maximise the benefit to patients. Key Words: Huge hepatocellular carcinoma, Hepatectomy, TACE.

Comparisons of Treatment for HER2-Positive Breast Cancer between Chinese and International Practice: A Nationwide Multicenter Epidemiological Study from China.

OBJECTIVE: To better understand the status of medical treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer and the differences between the Chinese and the international clinical practice. METHODS: This was a retrospective, nationwide, multicenter, epidemiological study of advanced breast cancer patients from China. Between January 01, 2012, and December 31, 2014, a total of 3649 patients, covering 7 geographic regions and 21 institutions, participated in this series of studies. HER2-positive breast cancer was selected among the group and adopted into this study. In comparison, we summarized the demographics and clinical characteristics of HER2-positive breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: A total of 918 patients diagnosed as HER2-positive breast cancer patients were included. The median age at diagnosis was 46 years (ranging, 23 to 78) with a single-peak incidence. The proportions of stages II-IV at diagnosis and distance metastasis in viscera were more than half of the participants. In comparison, the prevalence of estrogen or progesterone receptor-positive expression and luminalB subtype was relatively lower than that of the United States. The receipt of chemotherapy was fairly higher, while the usage of targeted therapy was seriously insufficient. Tumor size was in significantly positive associations with the duration of targeted therapy (Kendall's correlation coefficient = 0.3, P < 0.0001), while no prohibitive variables among clinical characteristics were detected. CONCLUSION: Our study suggested that HER2-positive breast cancer patients were characterized as a younger trend, a lower prevalence of hormonal receptor (HR)-positive expression, and less accessible to anti-HER2 targeted therapy with insufficient duration over the past few years in China. Concerted efforts should be exerted for promising survival benefits in the future. The trial registration number is https://clinicaltrials.gov/ct2/show/NCT03047889.

Immune implication of FAM83D gene in hepatocellular carcinoma.

FAM83D has been demonstrated to contribute to tumorigenesis. However, its immune effects in hepatocellular carcinoma (HCC) have not been reported. This study aimed to identify the immune role of FAM83D in HCC. FAM83D was over-expressed in HCC and contributed to poor prognosis according to the results of data analysis based on The Cancer Genome Atlas (TCGA). Afterward, the levels of immune cells infiltration were found to be correlated with the expression level of FAM83D in HCC. Through TISIDB and cBioPortal network tools, a total of 82 FAM83D-associated genes were screened out, including 12 immunoinhibitors, 20 immunostimulators and 50 tightly co-expressed genes. TCGA cohort was divided into train set and test set on the basis of the proportion of 7:3. According to FAM83D-associated immunomodulators, a four gene predicted model was established using train set via the Cox regression analysis. Survival analysis demonstrated that the overall survival (OS) of high-risk HCC patients was poor compared with the patients in low-risk group. The reliability and predicted power of the risk-score model were identified by a receiver operating characteristic (ROC) curve. A risk-score based nomogram as well as a calibration curve, which were created could be used to anticipate patient's 1-year, 3-year and 5-year survival probabilities. The test set was used to validate these results. Our findings showed that the FAM83D gene was related with HCC immunity. The immune marker chosen could be a promising biomarker for HCC prognosis.

Profile and outcome of receptor conversion in breast cancer metastases: a nation-wide multicenter epidemiological study.

Although receptor status including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) of the primary breast tumors was related to the prognosis of breast cancer patients, little information is yet available on whether patient management and survival are impacted by receptor conversion in breast cancer metastases. Using data from the nation-wide multicenter clinical epidemiology study of advanced breast cancer in China (NCT03047889), we report the situation of retesting ER, PR and HER2 status for breast cancer metastases and evaluate the patient management and prognostic value of receptor conversion. In total, 3295 patients were analyzed and 1583 (48.0%) patients retesting receptor status for metastasis. Discordance in one or more receptors between the primary and the metastatic biopsy was found in 37.7% of women. Patients who remained hormone receptor (HR) positive in their metastases had similar progression-free survival of first-line and second-line treatment compared to patients with HR conversion (P > .05). In multivariate analysis, patients who showed ER conversion from negative to positive had longer disease-free survival (DFS) than patients who remained negative in their metastases (hazard ratio, 2.05; 95% confidence interval [CI], 1.45-2.90; P < .001). Patients with PR remained positive and had longer DFS than patients with PR conversion from negative to positive (hazard ratio, 0.56; 95% CI, 0.38-0.83; P = .004). Patients with PR conversion have shorter overall survival than patients with PR remained positive or negative (P = .016 and P = .041, respectively). Our findings showed that the receptors' conversions were common in metastatic breast cancer, and the conversion impacted the survival.

Shikonin Ameliorates LPS-Induced Cardiac Dysfunction by SIRT1-Dependent Inhibition of NLRP3 Inflammasome.

Shikonin (SHI) is an anti-inflammatory agent extracted from natural herbs. It is still unknown whether SHI ameliorates lipopolysaccharide (LPS)-induced cardiac dysfunction. This study aims to explore the protective effects of SHI on LPS-induced myocardial injury and its mechanism. The LPS-induced cardiac dysfunction mouse model was employed to investigate the protective effects of SHI. In the present study, we found that SHI treatment improved the survival rate and cardiac function and remarkably ameliorated the release of inflammatory cytokines and macrophage infiltration in heart tissue of LPS-treated mice. SHI also reduced lactate dehydrogenase (LDH) and cardiac troponin (cTn) release, cell inflammation, and apoptosis in LPS plus adenosine triphosphate (ATP)-treated H9c2 cells. In addition, SHI significantly upregulated silent information regulator 1 (SIRT1) expression and suppressed the upregulation of NOD-like receptor protein 3 (NLRP3), cleaved caspase-1, and caspase-1 activity in heart tissues induced by LPS. Meanwhile, we got the same results in LPS plus ATP-treated H9c2 cells in vitro. Further, SIRT1 inhibitor or siRNA partially blocked SHI-mediated upregulation of SIRT1 expression and downregulation of NLRP3, cleaved caspase-1, and caspase-1 activity in heart tissues induced by LPS. Therefore, we conclude that SHI ameliorates LPS-induced cardiac dysfunction by inhibiting SIRT1-dependent activation of NLRP3 inflammasomes and might be a promising therapeutic strategy for the treatment of LPS-induced cardiac dysfunction.

MONARCH plus: abemaciclib plus endocrine therapy in women with HR+/HER2- advanced breast cancer: the multinational randomized phase III study.

AIM: To compare the efficacy, safety, and tolerability of abemaciclib plus endocrine therapy (ET) versus ET alone in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) from China, Brazil, India, and South Africa. METHODS: This randomized, double-blind, phase III study was conducted between 9 December 2016 and 29 March 2019. Postmenopausal women with HR-positive, HER2-negative ABC with no prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) received abemaciclib (150 mg twice daily) or placebo plus: anastrozole (1 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg per label) (cohort B). The primary endpoint was progression-free survival (PFS) in cohort A, analyzed using the stratified log-rank test. Secondary endpoints were PFS in cohort B (key secondary endpoint), objective response rate (ORR), and safety. This interim analysis was planned after 119 PFS events in cohort A. RESULTS: In cohort A, 207 patients were randomly assigned to the abemaciclib arm and 99 to the placebo arm. Abemaciclib significantly improved PFS versus placebo (median: not reached versus 14.7 months; hazard ratio 0.499; 95% confidence intervals (CI) 0.346-0.719; p = 0.0001). ORR was 65.9% in the abemaciclib arm and 36.1% in the placebo arm (p < 0.0001, measurable disease population). In cohort B, 104 patients were randomly assigned to the abemaciclib arm and 53 to the placebo arm. Abemaciclib significantly improved PFS versus placebo (median: 11.5 versus 5.6 months; hazard ratio 0.376; 95% CI 0.240-0.588; p < 0.0001). ORR was 50.0% in the abemaciclib arm and 10.5% in the placebo arm (p < 0.0001, measurable disease population). The most frequent grade ⩾3 adverse events in the abemaciclib arms were neutropenia, leukopenia, and anemia (both cohorts), and lymphocytopenia (cohort B). CONCLUSION: The addition of abemaciclib to ET demonstrated significant and clinically meaningful improvement in PFS and ORR, without new safety signals observed in this population.Trial Registration: ClinicalTrials.gov identifier: NCT02763566.

[Effects of Different Rotation Patterns of Oil-Rice on Methane and Nitrous Oxide Emissions in Rice Fields].

A field experiment was carried out to investigate the effects of different rice-rape rotation systems on methane and nitrous oxide emissions, which were measured using the static chamber/gas chromatography method, prediction of their global warming potentials (GWP), and greenhouse gas intensity (GHGI) in paddy fields. The results showed that the average cumulative emissions of CH4from a double cropping paddy field, single season rice field (including middle or late), rape field, and leisure land were 135.25, 55.64, 5.05, and 1.89 kg ·hm-2, respectively. The CH4 emission during the rice season accounted for 91.8%-98.5% of the annual CH4 emission in different rotation years, and the contents of dissolved organic carbon in paddy soil exhibited a significantly positive correlation with CH4 emission. The CH4 emission in conventional late rice paddy was 18.7% higher than that of hybrid late rice paddy (P<0.05). The average cumulative emissions of N2O from double cropping paddy field, single season rice field (including middle or late), rape field, and leisure land were 0.94, 0.64, 1.38, and 0.24 kg ·hm-2, respectively. Out of the total annual N2O emission, 57.2% to 70.2% was from the rape field; 17.8% and 30.6% was due to the winter fallow treatments with previous crop type of double corpping rice and single season rice, respectively. There was no significant difference in N2O emission between hybrid rice and conventional rice paddy fields. The GWP of double cropping rice-winter fallow and double cropping rice-rape was higher than that of rice-rape and rice-winter fallow, and the GWP of CH4 in rice season accounted for 71.2% to 90.9% of the annual GWP of rotation. The highest treatment of GHGI was rice-rice-rape, and the treatment of rice-oil and rice-winter slack was lower. According to the comprehensive environmental and economic benefits, the late hybrid rice-rape patterns should be selected to reduce greenhouse gases in multiple cropping rice fields of South China.

Aetiology of superficial fungal infections of the foot in urban outpatients in mainland China: A multicentre, prospective case study.

BACKGROUND: In China, the prevalence of superficial fungal infections of the foot is high and recurrence is common. However, a prospective, large-scale and multicentre study on the aetiology of superficial fungal infections of the foot is still lacking. OBJECTIVES: To study the epidemiology of aetiological agents of superficial fungal infections of the foot in urban outpatients in mainland China, as well as to understand the aetiology features of the pathogenic agent. METHODS: The study was designed as a multicentre, prospective epidemiological survey. A total of 1704 subjects were enrolled from seven geographical areas in mainland China. For each subject, one mycological sample and one bacterial sample were collected. KOH wet mount examination and culture were performed at local laboratories. The bacterial results were only reported in those with positive mycology. Further morphological identification and, if necessary, molecular biological identification were conducted in a central laboratory. RESULTS: Of 1704 enrolled subjects, 1327 (77.9%) subjects had positive fungal culture results. The incidence of dermatophytes, yeasts and moulds was 90.1%, 8.1% and 1.1%, respectively. The most frequently isolated aetiological agent (fungus) was Trichophyton rubrum. Moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections. The most frequently isolated bacterial genus in patients was Staphylococcus. CONCLUSION: This study prospectively investigated the clinical and mycological features of human dermatophytosis in mainland China. T rubrum was the most frequently isolated fungus, and moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections.

Brucea javanica Increases Survival and Enhances Gemcitabine Efficacy in a Patient-derived Orthotopic Xenograft (PDOX) Mouse Model of Pancreatic Cancer.

BACKGROUND/AIM: Traditional Chinese medicine (TCM) Brucea javanica (BJO) has shown anti-proliferation efficacy on human carcinoma cells in vitro. The aim of the present study was to evaluate for the first time the efficacy of BJO combined with the first-line chemotherapeutic drug gemcitabine (GEM) on tumor growth-inhibition and survival in a pancreatic cancer patient-derived orthotopic xenograft (PDOX) mouse model. MATERIALS AND METHODS: The pancreatic cancer tumor fragment originated from a patient at the Hefei First People's Hospital (Anhui, PR China). The surgical specimen was transplanted orthotopically in nude mice using surgical orthotopic implantation (SOI). All mice were randomized and assigned to 5 groups: G1: saline vehicle (0.1ml per mouse, oral, once per day); G2: GEM [100 mg/kg, intraperitoneal (i.p), twice per week]; G3: GEM+BJO [100 mg/kg GEM, i.p, twice per week+1g/kg BJO, oral, once per day (qd)]; G4: BJO (1g/kg, oral, qd). Group 5 and Group 6 were used to observe survival [G5: saline vehicle (0.1ml per mouse, oral, qd), G6: BJO (1g/kg, oral, qd)]. Body weight and tumor volume were measured twice per week. TUNEL staining was used to determine apoptosis. RESULTS: The combination of GEM + BJO resulted in a reduced tumor growth rate (p<0.05) and greater apoptosis (p<0.05) compared to the vehicle control and GEM monotherapy. In addition, the BJO-treated group showed a statistically significant increase in survival compared to the vehicle control (p<0.05). CONCLUSION: BJO is a promising non-toxic TCM to effectively treat pancreatic cancer, both as monotherapy and in combination with first-line GEM therapy.

Sorafenib in the treatment of patients with hepatocellular carcinoma (HCC) and microvascular infiltration: a systematic review and meta-analysis.

OBJECTIVE: Microvascular invasion is shown to be an independent risk factor for liver cancer recurrence. Timely treatment may reduce the recurrence rate and prolong total survival time. The aim of this study was to investigate the effectiveness of sorafenib in treating patients with hepatocellular carcinoma (HCC) and microvascular invasion. METHODS: A comprehensive literature search was conducted in PubMed, EMBASE, MEDLINE, web of science and Cochrane Library databases for articles published up to December 2019. Two researchers independently reviewed and cross-checked independent reports with sufficient information. A meta-analysis was conducted to assess the impact of sorafenib on mortality in patients with HCC and microvascular involvement. RESULTS: Four studies were included in the qualitative and quantitative analyses, comprising 955 cancer events and 505 cancer deaths. Meta-analyses showed that sorafenib treatment was associated with an improved survival rate versus no sorafenib treatment in patients with HCC and microvascular invasion (relative risk 1.369, 95% confidence interval 1.193, 1.570). CONCLUSIONS: Sorafenib treatment may improve survival in patients with HCC and microvascular invasion. However, due to the potential for residual confounding, the results should be interpreted with caution.

TNF-α regulates the early development of avascular necrosis of the femoral head by mediating osteoblast autophagy and apoptosis via the p38 MAPK/NF-κB signaling pathway.

Previous studies have shown that the tumor necrosis factor-α (TNF-α) levels in serum and bone tissues formed in avascular necrosis of femoral head (ANFH) patients were higher than those of normal individuals, indicating TNF-α might play a role in the pathogenesis of ANFH. However, the underlying mechanisms remain unclear. Hematoxylin and eosin staining was performed to show the pathological changes of ANFH bone tissues. TNF-α expression in normal and ANFH tissues was examined by quantitative real-time polymerase chain reaction and western blot analyses. Osteoblast autophagy and apoptosis, as well as signaling pathways activation, were measured by their corresponding marker proteins. Osteoblast proliferation, autophagy, and apoptosis were evaluated using cell counting kit-8, transmission electron microscopy, and flow cytometry. The structures of bone tissues of ANFH were obviously damaged. TNF-α expression was significantly upregulated in ANFH bone tissues compared to normal tissues. Autophagy and apoptosis were remarkably promoted, and p38 mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) signaling pathways were markedly activated in ANFH. Suppression of the p38 MAPK/NF-κB pathway significantly attenuated the TNF-α-induced autophagy, however, enhanced the TNF-α-induced apoptosis in osteoblasts. Increased TNF-α in ANFH regulated osteoblast autophagy and apoptosis by p38 MAPK/NF-κB signaling pathways, blocking the pathway by inhibitors exacerbated TNF-α-induced apoptosis through impairing autophagy flux.

Serum Carbohydrate Antigen 199 as a Biomarker for Evaluating Patients with Choledocholithiasis.

AIMS: Choledocholithiasis is a common and yet potentially debilitating disease of the biliary tract. While certain patients with this disease remain largely asymptomatic or experience mild discomfort, in several cases, patient can suffer biliary inflammation and other serious symptoms. Previous studies have detected elevated serum levels of carbohydrate antigen 199 in patients with choledocholithiasis. We wanted to know whether serum CA199 level in patients with choledocholithiasis is related to the level of inflammation in patients. METHODS: In the present study, we separated a cohort of 135 choledocholithiasis patients into two groups based on their white blood cell counts, which were either 3.5 - 9.5 × 109/L or ≥9.5 × 109/L. We also divided patients into two groups according to CPR < 10 mg/L and CRP ≥ 10 mg/L. At the same time, the correlation between CA199 and CRP level was analyzed. RESULTS: We then used a Rank-sum test to compare serum carbohydrate 199 levels between these groups, revealing significantly higher levels of this antigen in patients with a white cell count ≥9.5 × 109/L (Z = -3.584, P < 0.01). The two groups were grouped by CRP, and the CA199 level was compared. The difference between the two groups was statistically significant (P < 0.01). The correlation analysis between CA199 and CRP showed an obvious correlation (r = 0.574). CONCLUSION: This suggests that in patients with choledocholithiasis, higher circulating carbohydrate antigen 199 levels may correspond to a higher degree of inflammation.

Transcranial Direct Current Stimulation Ameliorates Cognitive Impairment via Modulating Oxidative Stress, Inflammation, and Autophagy in a Rat Model of Vascular Dementia.

To investigate the potential applications and the molecular mechanisms of transcranial direct current stimulation (tDCS) on cognitive impairment in a vascular dementia (VD) animal model. Sprague-Dawley rats were used in this study. VD rat model was induced by modified permanent bilateral common carotid artery occlusion (2-VO) approach. Anodal tDCS was applied to the animals. Morris water maze was used to analyze spatial memory and navigation ability. The pathological changes in the hippocampal CA1 region and cerebral cortex were examined via Hematoxylin-Eosin staining. The rats were sacrificed for the measurement of the level of superoxide (SOD), glutathione (GSH), reactive oxidative species (ROS), malondialdehyd (MDA), Interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α level in the hippocampus. Western blot was carried out to measure the hippocampal expression of microtubule-associated protein 1 light chain 3 (LC-3) and p62. Rats with VD have decreased number of neurons in the hippocampus and cerebral cortex, as well as worse cognitive impairment. The proliferation of activated microglia and astroglia, accompanied with attenuation of myelination were observed in the white matter about 1 month after 2-VO operation. These abnormalities were significantly ameliorated by tDCS treatment. Further study revealed that anodal tDCS could suppress the MDA and ROS level, while enhance the SOD and GSH level to reduce the oxidative stress. Anodal tDCS could inhibit hypoperfusion-induced IL-1ß, IL-6, and TNF-α expression to attenuate inflammatory response in hippocampus. Moreover, anodal tDCS treatment could alleviate autophagy level. The study has demonstrated a possible therapeutic role of tDCS in the treatment of cognitive impairment in VD.