Bortezomib in previously treated phosphatase and tension homology-deficient patients with advanced intrahepatic cholangiocarcinoma: An open-label, prospective and single-centre phase II trial.

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) is characterized by a dismal prognosis with limited therapeutic alternatives. To explore phosphatase and tension homolog (PTEN) as a biomarker for proteasome inhibition in ICC, we conducted a phase II trial to assess the second-line efficacy of bortezomib in PTEN-deficient advanced ICC patients. METHODS: A total of 130 patients with advanced ICC in our centre were screened by PTEN immunohistochemical staining between 1 July 2017, and 31 December 2021, and 16 patients were ultimately enrolled and treated with single-agent bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day cycle. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1. RESULTS: The median follow-up was 6.55 months (95% confidence interval [CI]: 0.7-19.9 months). Among the 16 enrolled patients, the ORR was 18.75% (3/16) and the disease control rate was 43.75% (7/16). The median progress-free survival was 2.95 months (95% CI: 2.1-5.1 months) and the median overall survival (mOS) was 7.2 months (95% CI: 0.7-21.6 months) in the intent-to-treat-patients. Treatment-related adverse events of any grade were reported in 16 patients, with thrombopenia being the most common toxicity. Patients with PTEN staining scores of 0 were more likely to benefit from bortezomib than those with staining scores > 0. CONCLUSIONS: Bortezomib yielded an encouraging objective response and a favourable OS as a second-line agent in PTEN-deficient ICC patients. Our findings suggest bortezomib as a promising therapeutic option for patients with PTEN-deficient ICC. HIGHLIGHTS: There is a limited strategy for the second-line option of intrahepatic cholangiocarcinoma (ICC). This investigator-initiated phase 2 study evaluated bortezomib in ICC patients with phosphatase and tension homology deficiency. The overall response rate was 18.75% and the overall survival was 7.2 months in the intent-to-treat cohort. These results justify further developing bortezomib in ICC patients with PTEN deficiency.

Serum metabolome responses induced by long-term inoculation of suspended PM2.5 in chicken.

The adverse effects of exposure to fine particulate matter (PM2.5) on body health have attracted global public attention. However, there is limited research on PM2.5 in animal houses. Numerous studies have indicated that long-term exposure to high levels of PM2.5 can cause damage to multiple systems in animals. Poultry houses are one of the primary sources of PM2.5 emissions. However, there is limited research on the effects of PM2.5 exposure on poultry organisms. This study analyzed the histopathological changes in the lung tissue of poultry under PM2.5 exposure conditions. It used the LC-MS method to analyze the alterations in the serum metabolomic profile of poultry. This study confirmed that long-term exposure to high levels of PM2.5 had significantly reduced the growth performance of poultry. Histopathological slides of the lung tissue in chickens exposed to long-term retention of PM2.5 clearly showed significant damage. Furthermore, the serum metabolome analysis revealed significant changes in the serum metabolic profile of chickens exposed to long-term PM2.5 exposure. Specifically, there were notable alterations in the Glycerophospholipid metabolism, Steroid hormone biosynthesis, and Phenylalanine, tyrosine, and tryptophan biosynthesis pathways.

A Comparison of Robotic Versus Laparoscopic Distal Pancreatectomy for Benign or Malignant Lesions: A Meta-Analysis.

Background: The momentum of robotic surgery is increasing, and it has great prospects in pancreatic surgery. It has been widely accepted and expanding to more and more centers. Robotic distal pancreatectomy (RDP) is the most recent advanced minimally invasive approach for pancreatic lesions and malignancies. However, laparoscopic distal pancreatectomy (LDP) also showed good efficacy. We compared the effect of RDP with LDP using a meta-analysis. Methods: From January 2010 to June 2023, clinical trials of RDP versus LDP were determined by searching PubMed, Medline, and EMBASE. A meta-analysis was conducted to compare the effect of RDP with LDP. This meta-analysis evaluated the R0 resection rate, lymph node metastasis rate, conversion to open surgery rate, spleen preservation rate, intraoperative blood loss, postoperative pancreatic fistula, postoperative hospital stay, 90-day mortality rate, surgical cost, and total cost. Results: This meta-analysis included 38 studies. Conversion to open surgery, blood loss, and 90-day mortality in the RDP group were all significantly less than that in the LDP group (P < .05). There was no difference in lymph node resection rate, R0 resection rate, or postoperative pancreatic fistula between the two groups (P > .05). Spleen preservation rate in the LDP group was higher than that in the RDP group (P < .05). Operation cost and total cost in the RDP group were both more than that in the LDP group (P < .05). It is uncertain which group has an advantage in postoperative hospital stay. Conclusions: To some degree, RDP and LDP were indeed worth comparing in clinical practice. However, it may be difficult to determine which is absolute advantage according to current data. Large sample randomized controlled trials are needed to confirm which is better treatment. PROSPERO ID: CRD4202345576.

Hypoxia-induced circRTN4IP1 promotes progression and glycolysis of hepatocellular carcinoma cells.

Hypoxia is one of the hallmarks of solid tumors, especially in hepatocellular carcinoma (HCC). CircRNAs are reported to be tightly connected to hypoxia and also have essential roles in cancer progression. However, many circRNAs implicated in hypoxia-mediated HCC progression are still unclear and require further exploration. In this study, a hypoxia cell model was structured by exposing cells to hypoxia conditions (1% O2) and normoxia conditions (21% O2) as a control. The effects of hypoxia and normoxia on cell viability, migration, invasion, and glycolysis were examined. The expressions of circRNARTN4IP1 under hypoxia were identified. Finally, molecular mechanisms and biological function of circRTN4IP1 were explored. We confirmed that hypoxia treatment facilitated capacities of proliferation, migration, invasion, and glycolysis in tumor cells. Hypoxia induced a significant increase expression of circRTN4IP1 in cells. Functionally, knockdown of circRTN4IP1 inhibited cell malignant progression and glycolysis under hypoxia HCC cells. Mechanistically, HIF1A targeted the promoter region of circRTN4IP1 and positively regulated the expression of circRTN4IP1. In addition, circRTN4IP1 targeted miR-532-5p/G6PC3 axis. In short, hypoxia induced activation of the HIF1A/circRTN4IP1/miR-532-5p/G6PC3 signaling axis, which promoted proliferation, migration, invasion, and glycolysis of HCC cells. This study may reveal a possible mechanism driving the progression of hypoxia HCC, so as to find potential effective candidates for targeting hypoxia microenvironment therapy.

Advanced renal pelvis carcinoma patient with an ERBB2 insertion mutation: a case report.

The prognosis of renal pelvis cancer is poor and therapeutic options are limited, especially for patients with advanced disease. In this report, we present a case of advanced renal pelvis carcinoma in a male patient in his 60s, characterized by an activating mutation in ERBB2. Clinical evaluation resulted in a pathological diagnosis of renal pelvis carcinoma with liver metastasis. Immunohistochemistry staining results suggested that CK, P63, and PAX8 were positively expressed, while Sy, CK7, CK20, S100, PAX8, and HEP1 were negatively expressed. Furthermore, next-generation sequencing results showed an activating mutation in the ERBB2 gene. The patient initially received a trastuzumab-based combination therapy, which led to a significant reduction in ERBB2 mutation frequency and a stable condition after three treatment cycles. However, following continuous treatment for 4 months, the patient developed drug resistance that resulted in disease relapse. Subsequently, the patient received apatinib treatment, but the therapeutic response was not satisfactory. The patient's condition underwent rapid deterioration and he ultimately succumbed to the disease. This case underscores the potential benefit of trastuzumab for treating ERBB2-mutated advanced renal pelvis cancer, but further highlights that overcoming drug resistance remains a crucial challenge for long-term efficacy.

Combined 16S and Internal Transcribed Spacer analysis revealed the effect of time on microbial community in animal house.

The outbreak of COVID-19 reminds people that aerosols have an important impact on health. The concentration and composition of microbial aerosol in livestock and poultry houses are closely related to the environmental conditions of livestock and poultry houses, and also related to the healthy growth of livestock and poultry. In our study, 16S and ITS sequencing techniques were used to analyze the relation and difference of bacteria and fungi in the air samples of a chicken house. At the age of 7 to 42 d, the operation classification unit (OTU) numbers of bacteria and fungi identified in our results were 2,398 and 986, respectively, of which the shared OTU numbers were 410 and 141, respectively. At the phylum level, Firmicutes, Proteobacteria, and Actinomycetes were the 3 most abundant bacterial phyla, and Ascomycetes and Basidiomycetes were the top 2 phyla in fungi. At the genus level, 7 differential fungal genera were identified, including Debaryomyces, Trichosporon, Wallemia, Aspergillus, Nigrospora, Fusarium, and Vishniacozyma. Compared with other bacterial genera, Lactobacillus, Cetobacterium, and Romboutsia had the highest abundance (more than 5%). The result showed that the Alpha diversity and Beta diversity of fungi were significantly different in different growing periods. However, only Beta diversity showed significant differences among bacteria. In general, the bacterial and fungal diversity of microbial aerosols in the chicken house increased significantly at the age of 7 to 42 d. And the evenness and richness of airborne fungal communities also increased obviously. In a word, we must pay attention to the complex community composition in the chicken house, this is closely related to animal health and the health of surrounding residents. The cooperation and communication between bacteria and fungi in PM2.5 samples provides a new reference to analyze the influence of microbial aerosol.

Non-cirrhotic portal hypertension secondary to cholangiointestinal anastomotic stricture after choledochal cyst excision: a case report.

Background: Cystectomy accompanied by biliary system reconstruction is an important treatment option for choledochal cysts, but the risk of post-operative complications is high. The most famous long-term complication is anastomotic stricture, whereas non-cirrhotic portal hypertension secondary to cholangiointestinal anastomotic stricture is rare. Case summary: Here we report the case of a 33-year-old female patient with a type I choledochal cyst who underwent choledochal cyst excision with Roux-en-Y hepaticojejunostomy. Thirteen years later, the patient presented with severe esophageal and gastric variceal bleeding, splenomegaly, and hypersplenism. Furthermore, cholangiointestinal anastomotic stricture with cholangiectasis was identified on imaging. A pathological examination of the liver suggested intrahepatic cholestasis, but the fibrosis was mild and inconsistent with severe portal hypertension. Therefore, the final diagnosis was portal hypertension secondary to a cholangiointestinal anastomotic stricture after choledochal cyst surgery. Fortunately, the patient recovered well after endoscopic treatment and dilated cholangiointestinal anastomotic stricture. Conclusion: Choledochal cyst excision with Roux-en-Y hepaticojejunostomy is the recommended standard of care for type I choledochal cysts; however, the long-term risk of cholangiointestinal anastomotic stricture requires consideration. Moreover, cholangiointestinal anastomotic stricture can lead to portal hypertension, and the degree of elevated portal pressure may be inconsistent with the degree of intrahepatic fibrosis.

Study on discharge characteristics of six-gap gas switch with corona assisted triggering.

To improve the triggering characteristics of the gas switch used for linear transformer driver, a method of corona assisted triggering based on the pre-ionization in switch gaps is proposed and applied to a six-gap gas switch. The principle is demonstrated by electrostatic field analysis and verified by the experimental study on the discharge characteristics of the gas switch. The results indicate that when the gas pressure is 0.3 MPa, the self-breakdown voltage remains about ±80 kV, and its dispersivity is lower than 3%. The effect of corona assisted triggering on the triggering characteristics increases with the higher permittivity of the inner shield. The positive trigger voltage of the switch with the proposed method can be reduced from 110 to 30 kV at a charging voltage of ±80 kV when the jitter is equal to that of the original switch. There are no pre-fire or late-fire when the switch operates continuously for 2000 shots.

Clinical and biomarker analyses of sintilimab plus gemcitabine and cisplatin as first-line treatment for patients with advanced biliary tract cancer.

The prognosis of biliary tract cancer (BTC) remains unsatisfactory. This single-arm, phase II clinical trial (ChiCTR2000036652) investigated the efficacy, safety, and predictive biomarkers of sintilimab plus gemcitabine and cisplatin as the first-line treatment for patients with advanced BTCs. The primary endpoint was overall survival (OS). Secondary endpoints included toxicities, progression-free survival (PFS), and objective response rate (ORR); multi-omics biomarkers were assessed as exploratory objective. Thirty patients were enrolled and received treatment, the median OS and PFS were 15.9 months and 5.1 months, the ORR was 36.7%. The most common grade 3 or 4 treatment-related adverse events were thrombocytopenia (33.3%), with no reported deaths nor unexpected safety events. Predefined biomarker analysis indicated that patients with homologous recombination repair pathway gene alterations or loss-of-function mutations in chromatin remodeling genes presented better tumor response and survival outcomes. Furthermore, transcriptome analysis revealed a markedly longer PFS and tumor response were associated with higher expression of a 3-gene effector T cell signature or an 18-gene inflamed T cell signature. Sintilimab plus gemcitabine and cisplatin meets pre-specified endpoints and displays acceptable safety profile, multiomics potential predictive biomarkers are identified and warrant further verification.

Exploring the Microbial Community Structure in the Chicken House Environment by Metagenomic Analysis.

The environmental conditions of chicken houses play an important role in the growth and development of these animals. The chicken house is an essential place for the formation of microbial aerosols. Microbial aerosol pollution and transmission can affect human and animal health. In this work, we continuously monitored fine particulate matter (PM2.5) in the chicken house environment for four weeks and studied the microbial community structure in the aerosols of the chicken house environment through metagenomic sequencing. Our results found that bacteria, fungi, viruses, and archaea were the main components of PM2.5 in the chicken house environment, accounting for 89.80%, 1.08%, 2.06%, and 0.49%, respectively. Conditional pathogens are a type of bacteria that poses significant harm to animals themselves and to farm workers. We screened ten common conditional pathogens and found that Staphylococcus had the highest relative abundance, while Clostridium contained the most microbial species, up to 456. Basidiomycetes and Ascomycota in fungi showed dramatic changes in relative abundance, and other indexes showed no significant difference. Virulence factors (VF) are also a class of molecules produced by pathogenic microbes that can cause host diseases. The top five virulence factors were found in four groups: FbpABC, HitABC, colibactin, acinetobactin, and capsule, many of which are used for the iron uptake system. In the PM2.5 samples, eight avian viruses were the most significant discoveries, namely Fowl aviadovirus E, Fowl aviadovirus D, Avian leukosis virus, Avian endogenous retrovirus EAV-HP, Avian dependent parvovirus 1, Fowl adenovus, Fowl aviadovirus B, and Avian sarcoma virus. The above results significantly improve our understanding of the microbial composition of PM2.5 in chicken houses, filling a gap on virus composition; they also indicate a potential threat to poultry and to human health. This work provides an important theoretical basis for animal house environmental monitoring and protection.

Research progress on distribution and exposure risk of microbial aerosols in animal houses.

Environmental aerosols in animal houses are closely related to the productive performance and health level of animals living in the houses. Preferable housing environments can improve animal welfare and production efficiency, so it is necessary to monitor and study these environments. In recent years, there have been many large-scale outbreaks of respiratory diseases related to biological aerosols, especially the novel coronavirus that has been sweeping the world. This has attracted much attention to the mode of aerosol transmission. With the rapid development of large-scale and intensive breeding, microbial aerosols have gradually become the main factor of environmental pollution in animal houses. They not only lead to a large-scale outbreak of infectious diseases, but they also have a certain impact on the health of animals and employees in the houses and increase the difficulty of prevention and control of animal-borne diseases. This paper reviews the distribution, harm, and control measures of microbial aerosols in animal house environments in order to improve people's understanding of them.

HAIC versus TACE for patients with unresectable hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) and Transarterial chemoembolization (TACE) both showed good local efficacy in advanced or unresectable hepatocellular carcinoma (HCC). We performed a systematic review and meta-analysis to compare the effect of HAIC with TACE in patients with unresectable HCC. METHODS: Clinical trials, which were about HAIC or TACE in Patients with unresectable HCC, were identified by searching PubMed, Medline, and EMBASE from January 2010 to March 2022. A meta-analysis was performed to analyze HAIC in comparison with TACE. Treatment response, 1-year overall survival (OS), 2-year OS and serious adverse events were evaluated in this meta-analysis. RESULTS: This meta-analysis included 6 studies. Objective response rate or Partial response in the HAIC group was significantly more than that in the TACE group (P < .05). But, stable disease showed no difference between the 2 groups (P = .52). Disease control rate in the HAIC group was better than that in the TACE group (P < .05). Progressive disease in the HAIC group was less than that in the TACE group (P < .05). In 1-year OS, there was no significant deterioration between the 2 groups (P = .53). There was not significant difference in 2-year OS between the 2 groups (P = .05). serious adverse events in the HAIC group was significantly less than that in the TACE group (P < .05). CONCLUSION: To some degree, HAIC may be a better therapeutic method in patients with unresectable HCC than TACE.

Optimized culture methods for isolating small extracellular vesicles derived from human induced pluripotent stem cells.

Extracellular vesicles that are derived from stem cells play an important role in the treatment of disease. To obtain high-quality small extracellular vesicles (sEVs), we optimized the culture conditions of human induced pluripotent stem cells (hiPSCs), the supernatant collection time, and sEVs extraction methods. Firstly, hiPSCs were cultured in extracellular vesicles-production medium (EVs-PM) containing different concentrations (0%, 0.25%, 0.5%, 2%, 5%, and 20%) of extracellular vesicle-depleted knockout serum replacement (ED-KSR), and the culture supernatants were collected continuously for 5 days. Then, the sEVs were isolated, followed by an evaluation of their characteristics. The survival rates of the hiPSCs lines that were cultured in EVs-PM containing 0.5% to 20% ED-KSR were not significantly different (P > 0.05). The survival rates of the hiPSCs in 0.5% ED-KSR after the culture supernatants were continuously collected for day 1, day 3, and day 5 were not statistically significant (P > 0.05). After 5 days of continuous collection of the supernatant, the hiPSCs expressed some pluripotent markers, while SSEA4 and TRA-1-60 expression changed gradually. The sEVs that were extracted by the two methods were all 50-200 nm, double-layered and oval or round cellular vesicles and expressed the marker proteins CD63, TSG101, and HSP70. The characteristics of sEVs extracted on day 1, day 3, and day 5 were almost identical on morphology, size and the relative quantity of annexin V-positive subpopulations. The PKH67 staining showed that the sEVs could be endocytosed by HepG2 cells and aggregated in the cytoplasm. The proliferation experiments showed that the sEVs can promote cell proliferation. In Conclusion, the 0.5% ED-KSR is the optimal concentration, and that the hiPSCs culture supernatant can be continuously collected for 5 days while maintaining high cell viability and some pluripotent characteristics. Both of the methods extraction can be used to obtain biologically active sEVs.

Chemoembolizing hepatocellular carcinoma with microsphere cored with arsenic trioxide microcrystal.

Chemoembolization for hepatocellular carcinoma (HCC) is often suboptimal due to multiple involved signaling and lack of effective drugs. Arsenic trioxide (ATO) is a potent chemotherapeutic agent, which can target multiple signaling and have substantial efficacy on HCC. However, its usage is limited due to systemic toxicity. Using ATO-eluting beads/microspheres for chemoembolization can have locoregional drug delivery and avoid systemic exposure but will require high drug load, which has not been achieved due to low solubility of ATO. Through an innovative approach, we generated the transiently formed ATO microcrystals via micronization and stabilized these microcrystals by solvent exchange. By encapsulating ATO microcrystals, but not individual molecules, with poly(lactide-co-glycolic acid) (PLGA), we developed microspheres cored with extremely high dense ATO. The molar ratio between ATO and PLGA was 157.4:1 and drug load was 40.1%, which is 4-20 fold higher than that of reported ATO nano/microparticles. These microspheres sustainably induced reactive oxygen species, apoptosis, and cytotoxicity on HCC cells and reduced tumor growth by 80% via locoregional delivery. Chemoembolization on mice model showed that ATO-microcrystal loaded microspheres, but not ATO, inhibited HCC growth by 60-75%, which indicates ATO within these microspheres gains the chemoembolizing function via our innovative approach.

Primary hepatic neuroendocrine carcinoma coexisting with distal cholangiocarcinoma: A case report and review of the literature.

INTRODUCTION: Although primary hepatic neuroendocrine carcinomas, whose prognostic mechanisms remain unclear, are rare, coexistence of neuroendocrine carcinomas and other tumors is rarer. In this report, we describe a unique case of coexistence between primary hepatic neuroendocrine carcinoma and a distal cholangiocarcinoma in the pancreas. PATIENT CONCERNS: A 64-year-old woman with a history of diabetes, but none of hepatitis, was admitted to hospital because of intermittent epigastric distension and pain discomfort for more than 1 month aggravated 1 day. A contrast-enhanced computed tomography (CT) scan of the upper abdomen and abdominal magnetic resonance imaging (MRI) revealed a thickening of the bile duct wall in the middle and lower segment of common bile duct and the corresponding lumen is narrow and low-density tumors with ring enhancement (1.83 cm × 1.9 cm) in lobi hepatis dexte. DIAGNOSIS: Primary neuroendocrine carcinoma of the liver was diagnosed to be coexisting with a distal cholangiocarcinoma, which had invaded the pancreas. Immunohistochemical examination revealed that the neoplastic cells strongly expressed chromogranin A, synaptophysin, and CD56 proteins. The tumor cells did not express HepPar-1, glypican-3, S-100, CK7, and CK19 in the liver tumor. A distal bile duct in pancreatic tissues shows the characteristics of typical bile duct carcinoma, as an invasion of carcinoma is also seen in the pancreatic tissues. Gastrointestinal endoscopy, chest and abdominal CT, abdominal MRI, and positron emission tomography (PET)-CT were used to exclude metastatic neuroendocrine tumors of the liver. INTERVENTIONS: Resection of the pancreas-duodenum, the right anterior lobe of the liver, and regional lymph nodes was performed in patients. OUTCOMES: The patient had survived for 5 months after the operation. CONCLUSION: A unique case of a coexistence of primary hepatic neuroendocrine carcinoma and a distal cholangiocarcinoma, which had invaded the pancreas. No treatment guidelines are established for the treatment of the unique case.

Development and evaluation of a time-saving RT-qRPA method for the detection of genotype 4 HEV presence in raw pork liver.

Hepatitis E virus (HEV) is a zoonotic pathogen spreading worldwide. Pig was known as its first and main animal reservoir. In China, pork consumption is very large and the risk of potential HEV contamination should not be underestimated. The present study aims to develop a quantitative real-time reverse transcription combining recombinase polymerase amplification assay (RT-qRPA) for the rapid detection of HEV RNA presence in raw pork liver on the Jinzhou markets in China. Methods: the specific primers and probes for RT-qRPA assay were designed targeting the ORF2/3 conserved region in genotype 4 swine HEV isolate (accession no. DQ279091.2) according to the TwistDx manual instructions. The specificity, sensitivity and reproducibility evaluations of the RT-qRPA method were subsequently conducted in assessing agreement with the standard RT-qPCR method. Results: the qRPA method step exhibited the obvious time-saving advantage which worked under the isothermal condition at 39 °C within about 30 min to complete the run while the compared standard qPCR method in the same cycle took almost 60 min to do. Both methods could exclusively detect the HEV genome equivalents from the quantified HEV-VLPs spiked samples. And both methods shared the same limit of detection (LOD) that was estimated at 1.25 × 103 genome equivalents copies/g spiked sample by the probit analysis. The recovery rate of HEV-VLPs reached a range of 9.56-14.65% by the RT-qRPA method which was higher than that of 1.34-2.34% by the standard RT-qPCR method. The detected HEV RNA positive rate in the field was 1.8% (1 out of 55) by both methods under Cohen's kappa statistic accessing with perfect agreement (κ = 1.00, p < 0.0005). The viral load in positive sample detected by the RT-qRPA method was estimated at 2.2125 × 105 genome copies/g pork liver sample. Conclusions, the present reported RT-qRPA method mainly targeting genotype 4 HEV is a rapid and reliable method. Its time-saving quality offers a promising for the development of a portable tool used in the routine monitoring of HEV contamination in the field.

Perioperative inhaled corticosteroids treatment is associated with decreased length-of-stay and direct medical costs in high-respiratory-risk surgeries.

Aims: To examine the impact of perioperative inhaled corticosteroids (ICS) on length-of-stay (LOS) and costs among patients receiving high-respiratory-risk surgeries.Methods: Adult patients who underwent high-respiratory-risk surgeries in 2015 were identified in the Tianjin Urban Employee Basic Medical Insurance database. Patients were grouped into ICS or non-ICS cohorts according to whether they received ICS during the perioperative period of the index hospitalization. Propensity Score Matching was performed to create matched pairs between two cohorts. The impact of perioperative ICS on LOS and direct medical costs was estimated by negative binomial model and generalized liner model.Results: Eight hundred and twenty-one hospital stays with high-respiratory-risk were selected in the ICS cohort and another 821 stays in the non-ICS cohort were matched. The mean LOS was 13.0 (±0.3) days in the ICS cohort, which was significantly lower than the matched non-ICS cohort. Patients with thorax and ear-nose-throat surgeries had a significant decrease in LOS in the ICS cohort compared to the non-ICS cohort, with a mean decrease of 5.5 and 1.1 days, respectively. In adjusted analyses, perioperative ICS treatment was associated with shorter LOS, lower total, and respiratory-related costs (reductions of 10.1%, 7%, and 5.3%, respectively) after controlling for demographic, clinical, and hospital characteristics.Limitations: Some respiratory risk factors such as living behavior and environment were unable to be captured and respiratory-related costs might be underestimated, limited by claim data. Lastly, caution should be taken when generalizing the results to other populations, as only patients with moderate-to-severe surgeries on the thorax and above were selected in this study.Conclusions: Perioperative ICS treatment was associated with decreased LOS and lower costs for patients undergoing high-respiratory-risk surgeries in China.

Polysaccharide from Phellinus Igniarius activates TLR4-mediated signaling pathways in macrophages and shows immune adjuvant activity in mice.

Polysaccharide from Phellinus igniarius (PPI) is known for its immune-regulating effect with low toxicity. Toll like receptor 4 (TLR4) is important in both innate and adaptive immune responses and considered to be a promising target for new immune adjuvants. In this study, PPI was investigated for its effect on activating TLR4 in RAW264.7 and peritoneal macrophages. The adjuvant potential of PPI was evaluated in OVA-immunized mice. The results showed PPI treatment significantly increased the secretion and the mRNA expression of both MyD88 dependent and TRIF dependent cytokines. IRAK-1, a key molecule on the downstream of MyD88, was polyubiquitinated while IRF-3, another key molecule on the downstream of TRIF, was phosphorylated obviously after the treatment of PPI. The phosphorylation of molecules involved in both NF-κB pathway and MAPK pathway were significantly up-regulated after PPI treatment. In addition, the effects of PPI on the macrophages almost completely disappeared after treating the cells with the TLR4 antagonist TAK-242. Further in vivo results showed PPI significantly increased the serum OVA-specific antibody and the OVA-specific spleen cell proliferation. Taken together, PPI can specifically stimulate TLR4 and activate both MyD88 and TRIF pathways. PPI has immune adjuvant activity and may become a new potential immune adjuvant.

Negative impact of hepatitis B surface seroclearance on prognosis of hepatitis B-related primary liver cancer.

AIM: To assess the impact of hepatitis B surface (HBsAg) seroclearance on survival outcomes in hepatitis B-related primary liver cancer. METHODS: Information from patients with hepatitis B-related liver cancer admitted in our hospital from 2008-2017 was retrieved. Cases diagnosed with HBsAg (-) and HBcAb (+) liver cancer were included in the HBsAg seroclearance (SC) group. HBsAg (+) liver cancer patients strictly matched for liver cancer stage (AJCC staging system, 8th edition), Child-Pugh score, and first diagnosis/treatment method (surgery, ablation and TACE) were assigned to the HBsAg non-seroclearance (NSC) group. Then, clinical, pathological and survival data in both groups were assessed. RESULTS: The SC and NSC groups comprised of 72 and 216 patients, respectively. Patient age (P < 0.001) and platelet count (P = 0.001) in the SC group were significantly higher than those of the NSC group. SC group patients who underwent surgery had more intrahepatic cholangiocarcinoma (ICC) and combined HCC-CC (CHC) cases than the NSC group, but no significant differences in tumor cell differentiation and history of liver cirrhosis were found between the two groups. The numbers of interventional treatments were similar in both groups (4.57 vs 5.07, P > 0.05). Overall survival was lower in the SC group than the NSC group (P = 0.019), with 1-, 3-, and 5-year survival rates of 82.1% vs 85.1%, 43.2% vs 56.8%, and 27.0% vs 45.2%, respectively. Survival of patients with AJCC stage I disease in the SC group was lower than that of the NSC group (P = 0.029). CONCLUSION: Seroclearance in patients with hepatitis B-related primary liver cancer has protective effects with respect to tumorigenesis, cirrhosis, and portal hypertension but confers worse prognosis, which may be due to the frequent occurrence of highly malignant ICC and CHC.