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Abstract Background LncRNAs are critical regulators of bladder cancer (BLCA), and ferroptosis is a newly discovered cell death responsible for mediating apoptosis and tumorigenesis. The present study aims to establish a prognostic signature of differentially expressed ferroptosis-related lncRNAs (DEFRlncRNAs) and explore the DEFRlncRNA associated with NUPR1 in BLCA. Methods DEFRlncRNAs in BLCA patients were screened using univariate and multivariate Cox and LASSO regression analyses. In vitro experiments were performed to detect the regulatory effects of DEFRlncRNAs on BLCA cells. A prognostic signature of DEFRlncRNAs in BLCA was created and validated. Moreover, we used RNA-binding protein immunoprecipitation (RIP) to evaluate the correlated DEFRlncRNA with NUPR1. Results A prognostic signature involving 18 DEFRlncRNAs in BLCA was created. Overexpression of AL355353.2 or knockdown of AL136084.3 promoted apoptosis in 5637 and T24 cells in vitro. Results from Starbase database estimated that AL136084.3 was positively associated with NUPR1 (R = 0.229, p

Abstract Background Ciprofol(HSK3486) is a novel 2,6-disubstituted phenol derivate, a short-acting intravenous sedative, which has similar efficacy characteristics as propofol with less incidence of side effect. Both ciprofol and propofol are often used in outpatient hysteroscopic surgery for sedation. However, the relative potency of these two drugs has not been fully determined in this context. Objective Our study aimed to investigate the potency-ratio of ciprofol and propofol under procedural sedation and anesthesia in restraining reaction of outpatient hysteroscopy dilatation. Methods The ED50 (effective dose in 50% of subjects) value for ciprofol and propofol were calculated by Up-and-Down Sequential Allocation Method. 60 healthy patients undergoing daytime hysteroscopy were randomly divided into two groups, which were intravenously injected with ciprofol at an initial dose of 0.4 mg/kg (group C) or propofol at an initial dose of 2 mg/kg (group P) at 2 min after intravenous injection of sufentanil 0.15ug/kg. A successful response is defined as the absence of patient movement in the case of cervical dilation. Conversely, the presence of patient movement is defined as failure. After successful or failed responses, each follow-up patient in the corresponding group was reduced or increased with propofol 0.5 mg/kg or ciprofol 0.1 mg/kg, respectively. Results The estimated ED50 value for ciprofol and propofol in restraining reaction of hysteroscopy dilatation was 0.444 mg/kg (95% CI, 0.385-0.503 mg/kg) and 1.985 mg/kg (95% CI, 1.801–2.170 mg/kg), respectively. The incidence of respiratory depression, hypoxemia and injection pain in ciprofol was significantly lower than those in propofol. Conclusion The ED50 of ciprofol and propofol in preventing hysteroscopy dilatation reaction was 0.444 mg/kg (95% CI, 0.385-0.503 mg/kg) and 1.985 mg/kg (95% CI, 1.801–2.170 mg/kg) for outpatient hysteroscopy. The potency-ratio of ciprofol and propofol observed in our study was 1.0:4.5(95%CI,1:3.9-1:5.1). Trial registration The study was registered at Chinese Clinical Trial Registry http//www.chictr.org.cn/ (Registration date19/11/22 Trial ID ChiCTR2200065954).

Abstract Liver metastases are commonly detected in the advanced stages of various malignant tumors, representing a significant clinical challenge. Throughout the process of liver metastases formation, immune cells play a pivotal role, particularly in the pre-metastatic and metastatic niches within the liver. Immune cells establish extensive and intricate interactions with tumor cells and other components in the liver, collectively promoting and sustaining the growth of liver metastases. Despite the limited efficacy of existing therapeutic modalities against some advanced liver metastases, novel immune-based treatment approaches are continuously being explored and validated. Building on the systematic elucidation of the immunosuppressive characteristics of liver metastases, we explored the potential of novel immunotherapies applicable to patients with liver metastases from multiple dimensions.

Abstract The aims of our study were to examine whether initial or subsequent adiposity status had a greater effect on hypertension. We collected data in 1992 and again in 2007 from the same group of 597 individuals in the middle age. The subjects were classified into four groups: individuals with a normal body mass index (BMI) in 1992 and 2007 were in Group I; those with a normal BMI in 1992, but became overweight or obese in 2007 were in Group II; those who were overweight or obese in 1992, but had a normal BMI in 2007 were in Group III; and those who were overweight or obese in 1992 and 2007 were in Group IV. Their demographic data were recorded. The relationship between adiposity status and hypertension was analyzed using logistic regression model. The cumulative incidence of hypertension was 35.5%, 56.3%, 50.0%, and 65.1% for Group I to IV, respectively. Compared with Group I, after adjusted factors, the hazard ratio (HR) was 1.80 for Group II (P = .001), 1.40 for Group III (P = .150), and 2.31 for Group IV (P

Summary: Background: Masked hypertension is associated with target organ damage (TOD) and adverse health outcomes, but whether antihypertensive treatment improves TOD in patients with masked hypertension is unproven. Methods: In this multicentre, randomised, double-blind, placebo-controlled trial at 15 Chinese hospitals, untreated outpatients aged 30–70 years with an office blood pressure (BP) of

Abstract Background Targeting CD47/SIRPα axis has emerged as a promising strategy in cancer immunotherapy. Despite the encouraging clinical efficacy observed in hematologic malignancies through CD47-SIRPα blockade, there are safety concerns related to the binding of anti-CD47 antibodies to CD47 on the membrane of peripheral blood cells. Methods In order to enhance the selectivity and therapeutic efficacy of the antibody, we developed a humanized anti-CD47 monoclonal antibody called Gentulizumab (GenSci059). The binding capacity of GenSci059 to CD47 was evaluated using flow cytometry and surface plasmon resonance (SPR) methods, the inhibitory effect of GenSci059 on the CD47-SIRPα interaction was evaluated through competitive ELISA assays. The anti-tumor activity of GenSci059 was assessed using in vitro macrophage models and in vivo patient-derived xenograft (PDX) models. To evaluate the safety profile of GenSci059, binding assays were conducted using blood cells. Additionally, we investigated the underlying mechanisms contributing to the weaker binding of GenSci059 to erythrocytes. Finally, toxicity studies were performed in non-human primates to assess the potential risks associated with GenSci059. Results GenSci059 displayed strong binding to CD47 in both human and monkey, and effectively inhibited the CD47-SIRPα interaction. With doses ranging from 5 to 20 mg/kg, GenSci059 demonstrated potent inhibition of the growth of subcutaneous tumor with the inhibition rates ranged from 30.3% to complete regression. Combination of GenSci059 with 2.5 mg/kg Rituximab at a dose of 2.5 mg/kg showed enhanced tumor inhibition compared to monotherapy, exhibiting synergistic effects. GenSci059 exhibited minimal binding to hRBCs compared to Hu5F9-G4. The binding of GenSci059 to CD47 depended on the cyclization of N-terminal pyroglutamic acid and the spatial conformation of CD47, but was not affected by its glycosylation modifications. A maximum tolerated dose (MTD) of 450 mg/kg was observed for GenSci059, and no significant adverse effects were observed in repeated dosages up to 10 + 300 mg/kg, indicating a favorable safety profile. Conclusion GenSci059 selectively binds to CD47, effectively blocks the CD47/SIRPα axis signaling pathway and enhances the phagocytosis effects of macrophages toward tumor cells. This monoclonal antibody demonstrates potent antitumor activity and exhibits a favorable safety profile, positioning it as a promising and effective therapeutic option for cancer.

Transition metal oxides (TMOs) are important anode materials in sodium-ion batteries (SIBs) due to their high theoretical capacities, abundant resources, and cost-effectiveness. However, issues such as the low conductivity and large volume variation of TMO bulk materials during the cycling process result in poor electrochemical performance. Nanosizing and compositing with carbon materials are two effective strategies to overcome these issues. In this study, spherical MnFe2O4@xC nanocomposites composed of MnFe2O4 inner cores and tunable carbon shell thicknesses were successfully prepared and utilized as anode materials for SIBs. It was found that the property of the carbon shell plays a crucial role in tuning the electrochemical performance of MnFe2O4@xC nanocomposites and an appropriate carbon shell thickness (content) leads to the optimal battery performance. Thus, compared to MnFe2O4@1C and MnFe2O4@8C, MnFe2O4@4C nanocomposite exhibits optimal electrochemical performance by releasing a reversible specific capacity of around 308 mAh·g−1 at 0.1 A·g−1 with 93% capacity retention after 100 cycles, 250 mAh·g−1 at 1.0 A g−1 with 73% capacity retention after 300 cycles in a half cell, and around 111 mAh·g−1 at 1.0 C when coupled with a Na3V2(PO4)3 (NVP) cathode in a full SIB cell.

Abstract Background Hepatitis B core antibody (HBcAb) positivity is considered a prior hepatitis B virus (HBV) infection. However, little is known about the effect of HBcAb positivity on surgical safety for hilar cholangiocarcinoma (hCCA). The present study aims to investigate the role of HBcAb positivity on postoperative complications of hCCA. Methods A retrospective analysis was performed on the status of HBcAb positivity, liver fibrosis, perioperative surgical complications, and long‐term outcomes of hCCA patients with Hepatitis B surface antigen (HBsAg) negativity who underwent surgical treatment in Tongji Hospital from April 2012 to September 2019. Results HBcAb positivity with negative HBsAg occurs in 137 hCCA patients (63.1%). A total of 99 hCCA patients with negative HBsAg underwent extended hemihepatectomy, of whom 69 (69.7%) and 30 (30.3%) were HBcAb‐positive and HBcAb‐negative, respectively. Significant fibrosis was detected in 63.8% of the patients with HBcAb‐positive, which was markedly higher than those with HBcAb‐negative (36.7%) (p = 0.016). The postoperative complications and 90‐day mortality rates were 37.4% (37/99) and 8.1% (8/99), respectively. The incidence of postoperative complications in HBcAb‐positive patients (44.9%) was significantly higher than that in HBcAb‐negative patients (20.0%) (p = 0.018). All the patients who died within 30‐day after surgery were HBcAb‐positive. Multivariate analysis showed that the independent risk factors for complications were HBcAb positivity, preoperative cholangitis, portal occlusion >15 min, and significant fibrosis. There were no significant differences in recurrence‐free survival (RFS) and overall survival (OS) between HBcAb‐positive and HBcAb‐negative patients (p = 0.642 and p = 0.400, respectively). Conclusions HBcAb positivity is a common phenomenon in hCCA patients from China, a country with highly prevalent HBcAb positivity. The status of HBcAb‐positive markedly increases the incidence of postoperative complications after extended hemihepatectomy for hCCA patients.

BackgroundVentricular septal rupture (VSR) is a serious complication occurring after myocardial infarction (MI). Cardiogenic shock (CS) is a common complication of VSR and an important factor affecting its prognosis. CS can occur in either an immediate or delayed manner after VSR; however, studies on the risk factors associated with immediate or delayed CS are scarce.MethodsWe retrospectively studied patients diagnosed with VSR after MI and admitted to the West China Hospital between September 2009 and August 2023. Demographic data, medical history, physical examination results, electrocardiograms, and echocardiographic and hematological data were extracted from electronic medical records or archived records. CS was defined as hypotension (

BackgroundCombined immunotherapy has shown promising results in the treatment of advanced HCC, whereas the priority population that would respond to the combined immunotherapy is still elusive. In addition, HCC with asymptomatic hyperamylasemia was not reported previously.Case presentationAn aged patient was diagnosed as HCC with BCLC stage C (bone metastasis). Notably, this patient showed asymptomatic hyperamylasemia. The patient was then enrolled in a trial evaluating combined immunotherapy of anti-PD-1 antibody sintilimab (IBI308) plus anti-CTLA-4 antibody (IBI310) in advanced HCC. After being treated with combined immunotherapy, this patient rapidly achieved complete response (CR) according to mRECIST criteria or immune partial response (iPR) according to iRECIST criteria and maintain the CR state for more than 12 months. Interestingly, serum levels of amylase and lipase in this patient were reduced after treatment.ConclusionWe reported, for the first time, a case of metastatic HCC with asymptomatic hyperamylasemia, and suggested that HCC patients with asymptomatic hyperamylasemia may benefit from combined immunotherapy of anti-CTLA-4 and PD-1 antibodies.

Abstract Backgrounds Remarkable interindividual variability in clopidogrel response is observed, genetic polymorphisms in P2RY12 and its signal pathway is supposed to affect clopidogrel response in CHD patients. Methods 539 CHD patients treated with clopidogrel were recruited. The platelet reaction index (PRI) indicated by VASP-P level were detected in 12–24 h after clopidogrel loading dose or within 5–7 days after initiation of maintain dose clopidogrel. A total of 13 SNPs in relevant genes were genotyped in sample A (239 CHD patients). The SNPs which have significant differences in PRI will be validated in another sample (sample B, 300 CHD patients). Results CYP2C19*2 increased the risk of clopidogrel resistance significantly. When CYP2C19*2 and CYP2C19*3 were considered, CYP2C19 loss of function (LOF) alleles were associated with more obviously increased the risk of clopidogrel resistance; P2RY12 rs6809699C > A polymorphism was also associated with increased risk of clopidogrel resistance (AA vs CC: P = 0.0398). This difference still existed after stratification by CYP2C19 genotypes. It was also validated in sample B. The association was also still significant even in the case of stratification by CYP2C19 genotypes in all patients (sample A + B). Conclusion Our data suggest that P2RY12 rs6809699 is associated with clopidogrel resistance in CHD patients. Meanwhile, the rs6809699 AA genotype can increase on-treatment platelet activity independent of CYP2C19 LOF polymorphisms.

AIM: To investigate whether the microgravity environment is related to retinal damage.METHODS: Hanging-tail mice tests were used to simulate weightlessness. Light microscopy, and transmission electron microscopic examinations of the retinal tissue structure were used to observe morphological changes. Immunohistochemistry and Western blot analyses were performed to detect the molecular changes associated with the observations.RESULT: Light microscopy and transmission electron microscopy demonstrated that more dead cells were detected in the ganglion layer and inner nuclear layer cells. TNF-α and caspase-3 protein expression in the retinas of simulated microgravity groups were up-regulated compared with the ground-based control group.CONCLUSION: The results demonstrated that simulated microgravity produced severe pathological damage in the retinas of mice.

Introduction: Pharmacokinetic variability in disease state is common in clinical practice, but its underlying mechanism remains unclear. Recently, gut microbiota has been considered to be pharmacokinetically equivalent to the host liver. Although some studies have explored the roles of gut microbiota and host Cyp450s in drug pharmacokinetics, few have explored their effects on pharmacokinetic variability, especially in disease states. Objectives: In this study, we aim to investigate the effects of gut microbiota and host Cyp450s on pharmacokinetic variability in mice with non-alcoholic steatohepatitis (NASH), and to elucidate the contribution of gut microbiota and host Cyp450s to pharmacokinetic variability in this setting. Methods: The pharmacokinetic variability of mice with NASH was explored under intragastric and intravenous administrations of a cocktail mixture of omeprazole, phenacetin, midazolam, tolbutamide, chlorzoxazone, and metoprolol, after which the results were compared with those obtained from the control group. Thereafter, the pharmacokinetic variabilities of all drugs and their relations to the changes in gut microbiota and host Cyp450s were compared and analyzed. Results: The exposures of all drugs, except metoprolol, significantly increased in the NASH group under intragastric administration. However, no significant increase in the exposure of all drugs, except tolbutamide, was observed in the NASH group under intravenous administration. The pharmacokinetic variabilities of phenacetin, midazolam, omeprazole, and chlorzoxazone were mainly associated with decreased elimination activity in the gut microbiota. By contrast, the pharmacokinetic variability of tolbutamide was mainly related to the change in the host Cyp2c65. Notably, gut microbiota and host Cyp450s exerted minimal effects on the pharmacokinetic variability of metoprolol. Conclusion: Gut microbiota and host Cyp450s co-contribute to the pharmacokinetic variability in mice with NASH, and the degree of contribution varies from drug to drug. The present findings provide new insights into the explanation of pharmacokinetic variability in disease states.

ABSTRACT As the α-subunit of the high-affinity receptor for the Fc portion of immunoglobulin E (FcεRIα), FcεRIα plays a central role in IgE-mediated allergic disorders and in the immunity and immunopathology of some parasitic infections. FcεRIα is specifically expressed on basophils and mast cells, but the mechanism that controls FcεRIα expression in these cells is poorly understood. In this study, we found that the natural antisense transcript (NAT) of FcεRIα (FCER1A-AS) is co-expressed with the sense transcript (FCER1A-S) in both interleukin (IL)-3-induced FcεRIα-expressing cells and in the high FcεRIα-expressing cell line MC/9. When FCER1A-AS is selectively knocked down by the CRISPR/RfxCas13d (CasRx) approach in MC/9 cells, the expression of both FCER1A-S mRNA and proteins is markedly decreased. Furthermore, FCER1A-AS deficiency was also found to be associated with a lack of FCER1A-S expression in vivo. Correspondingly, homozygous mice deficient in FCER1A-AS demonstrated a similar phenotype to FCER1A knockout mice in Schistosoma japonicum infection and in IgE-FcεRIα-mediated cutaneous anaphylaxis. Thus, we uncovered a novel pathway for the control of FcεRIα expression by its co-expressed natural antisense transcript. IMPORTANCE FcεRIα is responsible for high-affinity binding with the Fc portion of IgE, which is critical for IgE-dependent disease responses such as allergy responses and anti-parasite immunity. FcεRIα is expressed on a few cell types, including mast cells and basophils. Although the expression of FcεRIα is known to be promoted by the IL-3-GATA-2 pathway during its differentiation, the mechanism by which FcεRIα expression is maintained remains unknown. In this study, we discovered that a natural antisense transcript, FCER1A-AS, is co-expressed with the sense transcript. The presence of FCER1A-AS is essential for sense transcript expression in mast cells and basophils, but not for the differentiation of these cells through cis-regulation. Like FcεRIα knockout mice, mice lacking FCER1A-AS also exhibit reduced survival after Schistosoma japonicum infection and a lack of IgE-mediated cutaneous anaphylaxis. Thus, a novel pathway for regulating IgE-mediated allergic diseases through noncoding RNAs has been revealed.

Abstract Background Hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) is heterogeneous and frequently contains multifocal tumors, but how the multifocal tumors relate to each other in terms of HBV integration and other genomic patterns is not clear. Methods To interrogate heterogeneity of HBV-HCC, we developed a HBV genome enriched single cell sequencing (HGE-scSeq) procedure and a computational method to identify HBV integration sites and infer DNA copy number variations (CNVs). Results We performed HGE-scSeq on 269 cells from four tumor sites and two tumor thrombi of a HBV-HCC patient. HBV integrations were identified in 142 out of 269 (53%) cells sequenced, and were enriched in two HBV integration hotspots chr1:34,397,059 (CSMD2) and chr8:118,557,327 (MED30/EXT1). There were also 162 rare integration sites. HBV integration sites were enriched in DNA fragile sites and sequences around HBV integration sites were enriched for microhomologous sequences between human and HBV genomes. CNVs were inferred for each individual cell and cells were grouped into four clonal groups based on their CNVs. Cells in different clonal groups had different degrees of HBV integration heterogeneity. All of 269 cells carried chromosome 1q amplification, a recurrent feature of HCC tumors, suggesting that 1q amplification occurred before HBV integration events in this case study. Further, we performed simulation studies to demonstrate that the sequential events (HBV infecting transformed cells) could result in the observed phenotype with biologically reasonable parameters. Conclusion Our HGE-scSeq data reveals high heterogeneity of HCC tumor cells in terms of both HBV integrations and CNVs. There were two HBV integration hotspots across cells, and cells from multiple tumor sites shared some HBV integration and CNV patterns.

Key points 1. The RAA with an enrichment step that utilizes magnetic beads coated with M1 protein. 2. A very effective method for detecting low-load virus in blood samples. 3. The first report describing virus detection using this method.

Abstract Background Ingestion of fish bones leading to gastric perforation and inducing abscess formation in the caudate lobe of the liver is very rare. Case presentation A 67-year-old man presented to our hospital with a 2-day history of subxiphoid pain. There were no specific symptoms other than pain. Laboratory tests showed only an increase in the number and percentage of neutrophils. Contrast-enhanced Computerized tomography (CT) of the abdomen showed two linear dense opacities in the gastric cardia, one of which penetrated the stomach and was adjacent to the caudate lobe of the liver, with inflammatory changes in the caudate lobe. We finally diagnosed his condition as a caudate lobe abscess secondary to intestinal perforation caused by a fishbone based on the history and imaging findings. The patient underwent 3D laparoscopic partial caudate lobectomy, incision and drainage of the liver abscess, and fishbone removal. The procedure was successful and we removed the fishbone from the liver. The patient was discharged on the 9th postoperative day without other complications. Conclusions Liver abscess caused by foreign bodies requires multidisciplinary treatment. Especially when located in the caudate lobe, we must detect and remove the cause of the abscess as early as possible. Foreign bodies that perforate the gastrointestinal tract can penetrate to the liver and cause abscess formation, as in this case. When exploring the etiology of liver abscesses, we should investigate the general condition, including the whole gastrointestinal tract.

BackgroundIntrahepatic cholangiocarcinoma (ICC) is a highly malignant biliary tumor. Patients with unresectable and advanced ICC have a poor prognosis with current gemcitabine-based chemotherapy. Combination therapy strategies based on immunotherapy have achieved promising results in various tumor types.Case presentationWe reported a patient with unresectable ICC who received lenvatinib and pembrolizumab in combination with gemcitabine plus cisplatin (GP) chemotherapy and subsequently underwent radical liver resection. A 46-year-old male with a history of chronic hepatitis B and hypertension was diagnosed with ICC. Multiple liver tumors with ring-like enhancement were detected on abdominal contrast-enhanced CT and MRI. Enlarged lymph nodes were found in the hilar and retroperitoneal areas. The tumor was clinically staged as T2N1M0 (stage IIIB). Lenvatinib and pembrolizumab in combination with GP chemotherapy were adopted as first-line treatments for the patient. After six cycles of scheduled treatment, the diameter of the largest liver lesion and the number of liver lesions were markedly reduced. The level of the tumor marker CA19-9 decreased to a normal range. A partial response according to the mRECIST criteria was achieved without severe toxicities. Non-anatomical liver resection (segment 4b, 5,6 + segment 7 + segment 8), cholecystectomy and hilar lymph node dissection were performed one month after stopping combination therapy. Pathological examination confirmed a diagnosis of moderate-to-poorly differentiated ICC with lymph node metastasis. The patient has survived 15 months following resection of the tumors, with no evidence of local recurrence or distant metastasis.ConclusionLenvatinib and anti-PD1 antibody pembrolizumab in combination with GP chemotherapy provided promising antitumor efficacy with reasonable tolerability, which may be a potentially feasible and safe conversion therapy strategy for patients with initially unresectable and advanced ICC.

Drug-induced cardiotoxicity (DICT) is an important concern of drug safety in both drug development and clinical application. The clinical manifestations of DICT include cardiomyopathy, arrhythmia, myocardial ischemia, heart failure, and a series of cardiac structural and functional changes. The occurrence of DICT has negative impacts on the life quality of the patients, brings additional social and economic burden. It is important to identify the potential factors and explore the mechanisms of DICT. Traditional cardiovascular risk factors can only partially explain the risk of DICT. Pharmacogenomic studies show accumulated evidence of genetics in DICT and suggest the potential to guide precision therapy to reduce risk of cardiotoxicity. The comprehensive application of technologies such as third-generation sequencing, human induced pluripotent stem (iPS) cells and genome editing has promoted the in-depth understanding of the functional role of susceptible genes in DICT. This paper reviewed drugs that cause DICT, the clinical manifestations and laboratory tests, as well as the related content of genetic variations associated with the risk of DICT, and further discussed the implication of new technologies in pharmacogenomics of DICT.

Abstract Hepatocellular carcinoma (HCC) is usually associated with varying degrees of cirrhosis. Among cirrhotic patients with solitary HCC in the absence of macro-vascular invasion, whether tumor size drives prognosis or not after hepatectomy remains unknown. This study aimed to investigate the prognostic impact of tumor size on long-term outcomes after hepatectomy for solitary HCC patients with cirrhosis and without macrovascular invasion. A total of 813 cirrhotic patients who underwent curative hepatectomy for solitary HCC and without macrovascular invasion between 2001 and 2014 were retrospectively studied. We set 5 cm as the tumor cut-off value. Propensity score matching (PSM) was performed to minimize the influence of potential confounders including cirrhotic severity that was histologically assessed according to the Laennec staging system. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after PSM. Overall, 464 patients had tumor size ≤ 5 cm, and 349 had tumor size > 5 cm. The 5-year RFS and OS rates were 38.3% and 61.5% in the ≤ 5 cm group, compared with 25.1% and 59.9% in the > 5 cm group. Long-term survival outcomes were significantly worse as tumor size increased. Multivariate analysis indicated that tumor size > 5 cm was an independent risk factor for tumor recurrence and long-term survival. These results were further confirmed in the PSM cohort of 235 pairs of patients. In cirrhotic patients with solitary HCC and without macrovascular invasion, tumor size may significantly affect the prognosis after curative hepatectomy.

Abstract Radioresistance continues to be the leading cause of recurrence and metastasis in nasopharyngeal cancer. Long noncoding RNAs are emerging as regulators of DNA damage and radioresistance. LINC-PINT was originally identified as a tumor suppressor in various cancers. In this study, LINC-PINT was significantly downregulated in nasopharyngeal cancer tissues than in rhinitis tissues, and low LINC-PINT expressions showed poorer prognosis in patients who received radiotherapy. We further identified a functional role of LINC-PINT in inhibiting the malignant phenotypes and sensitizing cancer cells to irradiation in vitro and in vivo. Mechanistically, LINC-PINT was responsive to DNA damage, inhibiting DNA damage repair through ATM/ATR-Chk1/Chk2 signaling pathways. Moreover, LINC-PINT increased radiosensitivity by interacting with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and negatively regulated the expression and recruitment of DNA-PKcs. Therefore, these findings collectively support the possibility that LINC-PINT serves as an attractive target to overcome radioresistance in NPC.

Abstract Background Pancreatic resections are complex and technically challenging surgical procedures. They often come with potential limitations to high-volume centers. Distal pancreatectomy is a relatively simple procedure in most cases. It facilitates the development of up-to-date minimally invasive surgical procedures in pancreatic surgery including laparoscopic distal pancreatectomy and robot-assisted distal pancreatectomy. Main body To obtain a desirable long-term prognosis, R0 resection and adequate lymphadenectomy are crucial to the surgical management of pancreatic cancer, and they demand standard procedure and multi-visceral resection if necessary. With respect to combined organ resection, progress has been made in evaluating and determining when and how to preserve the spleen. The postoperative pancreatic fistula, however, remains the most significant complication of distal pancreatectomy, with a rather high incidence. In addition, a safe closure of the pancreatic remnant persists as an area of concern. Therefore, much efforts that focus on the management of the pancreatic stump have been made to mitigate morbidity. Conclusion This review summarized the historical development of the techniques for pancreatic resections in recent years and describes the progress. The review eventually looked into the controversies regarding distal pancreatectomy for tumors in the body and tail of the pancreas.

Background: There exists no broad agreement of experts on the practice of pharmaceutical care for cancer pain management in outpatient clinics.Objectives: This study aimed to use the Delphi consensus process to provide expert recommendations on the practice of cancer pain management in outpatient clinics from the point of view of pharmaceutical care in clinical practice and future clinical trials.Methods: A comprehensive literature review was conducted to draft the initial practice. In this process, 30–40 senior experts from various provinces in China were invited to rank the items of practice during the two Delphi consultations. The definitions of consensus included a combination with an average score of ≥4, the percentage of experts rating the scores at >4 points, and the coefficient of variation of the scores.Results: The expert panel comprised 18 pharmacists, 3 anesthesiologists, 6 oncologists, and 9 nurses. As a result of a comprehensive review, 33 items were initially formed. Among them, the consensus was reached for 27 items after the first Delphi round. The other six items and a total of five items for supplementation entered the second round, among which consensus was reached for eight items and three items were excluded. Expert consensus was achieved on 35 items after two rounds of consultation, which involved the collection of patient basic information, comprehensive pain assessment, breakthrough or neuropathic pain assessment, analgesic treatment evaluation, out-of-hospital follow-up, medical records, and evidence-based documents for reference.Conclusion: The final list of 35 items could be used to develop the practice of pharmaceutical care for cancer pain management in outpatient clinics in China. The practice may aid in the standardization of pharmaceutical care for pain, relieve pain to the greatest extent possible, and enhance the level of pain management in China.

Abstract. Background. Resting heart rate (RHR) is considered as a strong predictor of total mortality and hospitalization due to heart failure in hypertension patients. Bisoprolol fumarate, a second-generation beta-adrenoreceptor blockers (β-blocker) is commonly prescribed drug to manage hypertension. The present study was to retrospectively evaluate changes in the average RHR and its association with cardiovascular outcomes in bisoprolol-treated coronary artery disease (CAD) patients from the CAD treated with bisoprolol (BISO-CAD) study who had comorbid hypertension. Methods. We performed ad-hoc analysis for hypertension sub-group of the BISO-CAD study (n = 866), which was a phase IV, multination, multi-center, single-arm, observational study carried out from October 2011 to July 2015 across China, South Korea, and Vietnam. Multivariate regression analysis was used to identify factors associated with incidence of composite cardiac clinical outcome (CCCO), the results were presented as adjusted odds ratio (OR) along with 95% confidence interval (CI) and adjusted P value. Results. A total of 681 patients (mean age: 64.77 ± 10.33 years) with hypertension from BISO-CAD study were included in the analysis. Bisoprolol improved CCCOs in CAD patients with comorbid hypertension, with RHR

Summary: Background: The impact of bile leakage (BL) on the long-term prognosis in patients with primary liver cancers after hepatectomy remains unclear. Methods: One thousand nine hundred and seventy-one consecutive patients with primary liver cancers who underwent curative hepatectomy were enrolled. 75 patients encountered BL, including 34 long-time BL (LTBL) and 41 short-time BL (STBL) according to 4-weeks demarcation. Variables associated with BL were identified using multiple logistic regression analysis. 75 patients without BL were enrolled into the Non-BL group using a one-to-one propensity score matched analysis before assessing the impact of BL on the long-term prognosis. The levels of interleukin-6 (IL-6) and C-reactive protein (CRP) in the serum and drain fluid were detected and compared. Results: The tumor size, type of liver cancer, operation time, blood loss and blood transfusion were independent risk factors for BL. The long-term survival showed no difference between the patients with and without BL (p > 0.05), while the LTBL was a significant predictor of poor long-term prognosis (p

AIM: To observe changes in the flash electroretinogram(ERG)and retinal microcirculation in mice suspended by their tails, an animal model that simulates cephalad movement of bodily fluids under conditions of microgravity.METHODS: Thirty-six adult male C57BL/6J mice(36 eyes)were randomly divided into three experimental groups and three control groups. Mice in the experimental groups were tail-suspended for 15d(Group one), tail-suspended for 30d(Group two), or tail-suspended followed by returning to normal position for 30d(Group three). Three control groups were similarly fixed with a harness but kept in the normal position for corresponding periods of 15, 30, and 60d. The mice were immediately examined using scotopic ERG(including oscillatory potentials \〖OPs\〗)and fundus fluorescein angiography(FFA)in vivo, and subsequently sacrificed to analyze the retinal histology(methods including immunohistochemistry and TUNEL staining)in vitro. Independent sample t-test was used for data comparison between the same time-point groups.RESULTS: Following 15-days' tail-suspension, scotopic ERG showed a decline in OPs, but not in the b-wave; the second OP(O2)showed an amplitude of 197±33μV, which was about 60% of the control level(t=-5.938, P2 showing an average value of 264±39μV; when compared to the corresponding control group(308±41μV), no significant difference was observed(t=-1.887, P>0.05). Morphologically, only the 15-days' tail-suspended mice showed FFA with microvascular dilation and tortuosity. Rhodopsin and cone-opsin were almost normal and no apoptotic-positive signals were detected in the retinas of the three tail-suspended groups.CONCLUSION: Simulating cephalad shifting of bodily fluids as under microgravity, using short-term tail-suspension can affect rodent ERG and retinal microcirculation; however, the change is reversible with no obvious permanent injury observed in the retinas.

Background. It is critical to accurately identify patients with severe acute pancreatitis (SAP) and moderately SAP (MSAP) in a timely manner. The study was done to establish two early multi-indicator prediction models of MSAP and SAP. Methods. Clinical data of 469 patients with acute pancreatitis (AP) between 2015 and 2020, at the First Affiliated Hospital of Fujian Medical University, and between 2012 and 2020, at the Affiliated Union Hospital of Fujian Medical University, were retrospectively analyzed. The unweighted predictive score (unwScore) and weighted predictive score (wScore) for MSAP and SAP were derived using logistic regression analysis and were compared with four existing systems using receiver operating characteristic curves. Results. Seven prognostic indicators were selected for incorporation into models, including white blood cell count, lactate dehydrogenase, C-reactive protein, triglyceride, D-dimer, serum potassium, and serum calcium. The cut-offs of the unwScore and wScore for predicting severity were set as 3 points and 0.513 points, respectively. The unwScore (AUC=0.854) and wScore (AUC=0.837) were superior to the acute physiology and chronic health evaluation II score (AUC=0.526), the bedside index for severity in AP score (AUC=0.766), and the Ranson score (AUC=0.693) in predicting MSAP and SAP, which were equivalent to the modified computed tomography severity index score (AUC=0.823). Conclusions. The unwScore and wScore have good predictive value for MSAP and SAP, which could provide a valuable clinical reference for management and treatment.

Background Dual antiplatelet therapy based on aspirin and P2Y12 receptor antagonists such as clopidogrel is currently the primary treatment for coronary artery disease (CAD). However, a percentage of patients exhibit clopidogrel resistance, in which genetic factors play vital roles. This study aimed to investigate the roles of GAS5 (growth arrest‐specific 5) and its rs55829688 polymorphism in clopidogrel response in patients with CAD. Methods and Results A total of 444 patients with CAD receiving dual antiplatelet therapy from 2017 to 2018 were enrolled to evaluate the effect of GAS5 single nucleotide polymorphism rs55829688 on platelet reactivity index. Platelets from 37 patients of these patients were purified with microbeads to detect GAS5 and microRNA‐223‐3p (miR‐223‐3p) expression. Platelet‐rich plasma was isolated from another 17 healthy volunteers and 46 newly diagnosed patients with CAD to detect GAS5 and miR‐223‐3p expression. A dual‐luciferase reporter assay was performed to explore the interaction between miR‐223‐3p and GAS5 or P2Y12 3′‐UTR in (human embryonic kidney 293 cell line that expresses a mutant version of the SV40 large T antigen) HEK 293T and (megakaryoblastic cell line derived in 1983 from the bone marrow of a chronic myeloid leukemia patient with megakaryoblastic crisis) MEG‐01 cells. Loss‐of‐function and gain‐of‐function experiments were performed to reveal the regulation of GAS5 toward P2Y12 via miR‐223‐3p in MEG‐01 cells. We observed that rs55829688 CC homozygotes showed significantly decreased platelet reactivity index than TT homozygotes in CYP2C19 poor metabolizers. Platelet GAS5 expression correlated positively with both platelet reactivity index and P2Y12 mRNA expressions, whereas platelet miR‐223‐3p expression negatively correlated with platelet reactivity index. Meanwhile, a negative correlation between GAS5 and miR‐223‐3p expressions was observed in platelets. MiR‐223‐3p mimic reduced while the miR‐223‐3p inhibitor increased the expression of GAS5 and P2Y12 in MEG‐01 cells. Knockdown of GAS5 by siRNA increased miR‐223‐3p expression and decreased P2Y12 expression, which could be reversed by the miR‐223‐3p inhibitor. Meanwhile, overexpression of GAS5 reduced miR‐223‐3p expression and increased P2Y12 expression, which could be reversed by miR‐223‐3p mimic. Conclusions GAS5 rs55829688 polymorphism might affect clopidogrel response in patients with CAD with the CYP2C19 poor metabolizer genotypes, and GAS5 regulates P2Y12 expression and clopidogrel response by acting as a competitive endogenous RNA for miR‐223‐3p.

BackgroundGrowing evidence suggests that circulating tumor cell (CTC) clusters may be an important factor in the metastatic process, but their role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to characterize the molecular and clinical features of CTC cluster-positive human HCC and to assess its prognostic value in HCC patients.MethodsThe CTCs and CTC clusters were evaluated in 204 HCC patients using CellSearch™ System. The counts of CTCs and CTC clusters were correlated with different clinical features, while their associations with progression-free survival (PFS) and overall survival (OS) were evaluated integrally and hierarchically by Kaplan–Meier estimates or Cox proportional regression analysis. Five cases each of CTC cluster-negative and cluster-positive patients were selected for RNA-sequencing analysis. The results of gene enrichment analysis were further verified using tissue microarray (TMA) by immunohistochemistry (IHC).ResultsCTCs and CTC clusters were detected in 76 (37.3%) and 19 (9.3%) of 204 preoperative samples, respectively. CTC cluster-positive HCC represented an aggressive HCC phenotype with larger tumor size, more frequent microvascular invasion, and higher tumor stages. The survival of HCC patients utilizing CTCs and CTC clusters individually showed prognostic significance, while joint analysis revealed patients in Group III (CTC ≥ 2 and CTC cluster > 0) had the worst outcome. Stratified analysis of outcomes in Barcelona Clinic Liver Cancer (BCLC) and tumor–node–metastasis (TNM) stages indicated that patients with CTC clusters had significantly poorer prognosis in each stage than those without CTC clusters. Moreover, the RNA sequencing and TMA staining results showed that CTC cluster-positive HCCs were usually associated with Wnt/β-catenin signaling activation.ConclusionThe presence of CTC clusters characterizes an aggressive HCC subtype. CTC clusters may be used as a biomarker in predicting the prognosis on each stage of malignancy in HCC, which provides evidence for formulating therapeutic strategies for more precise treatment.

BackgroundSelf-management of ambulatory cancer pain is full of challenges. Motivated by the need for better pain management, we developed a WeChat-supported platform, Medication Housekeeper (MediHK), to enhance communication, optimize outcomes, and promote self-management in the home setting. ObjectiveWe conducted a randomized controlled trial to assess whether the joint physician-pharmacist team through MediHK would provide better self-management of ambulatory patients with cancer pain. MethodsPatients were randomly assigned to either an intervention group or control group. During the 4-week study period, the pharmacist would send 24-hour pain diaries daily, adverse drug reaction (ADR) forms every 3 days, and the Brief Pain Inventory form every 15 days to patients in the intervention group via MediHK. If a patient needed a change in drug/dosage or treatment of an ADR after the comprehensive review, the pharmacist would propose pharmacological interventions to the attending physician, who was then responsible for prescribing or adjusting pain medications. If no adjustments were needed, the pharmacist provided appropriate targeted education based on knowledge deficits. Patients in the control group received conventional care and did not receive reminders to fill out the forms. However, if the control group patients filled out a form via MediHK, the pain management team would review and respond in the same way as for the intervention group. The primary outcomes included pain intensity and pain interference in daily life. Secondary outcomes included patient-reported outcome measures, medication adherence, ADRs, and rehospitalization rates. ResultsA total of 100 patients were included, with 51 (51%) in the intervention group and 49 (49%) in the control group. The worst pain scores, least pain scores, and average pain scores in the intervention group and the control group were statistically different, with median values of 4 (IQR 3-7) vs 7 (IQR 6-8; P=.001), 1 (IQR 0-2) vs 2 (IQR 1-3; P=.02), and 2 (IQR 2-4) vs 4 (IQR 3-5; P=.001), respectively, at the end of the study. The pain interference on patients' general activity, mood, relationships with others, and interests was reduced, but the difference was not statistically significant compared with the control group (Ps=.10-.76). The medication adherence rate increased from 43% to 63% in the intervention group, compared with an increase of 33% to 51% in the control group (P

Abstract Aberrant mechanical properties and immunosuppression are the two key factors that limit the antitumor efficacy of T cell immune checkpoint blockade inhibitors, e.g., programmed cell death‐1 antibody (PD‐1 Ab), against solid tumors in the clinic. This study leverages hyperbaric oxygen (HBO) for the first time to address these two issues and reports the PD‐1‐Ab‐mediated immune responses against various stroma‐rich solid malignancies. The results demonstrate that HBO promoted PD‐1 Ab delivery and T cells infiltration into tumor parenchyma by depleting the extracellular matrix's main components, such as collagen and fibronectin. Furthermore, HBO disrupts hypoxia‐mediated immunosuppression and helps PD‐1 Ab trigger robust cytotoxic T lymphocytes and long‐lasting immunological memory to inhibit tumor relapses. Such enhanced immune responses are effective in solid tumors from rodents and the cancer cells from hepatocellular carcinoma patients. The results illustrate that HBO bolsters antitumor efficacy of PD‐1 Ab, and the HBO–PD‐1 Ab combination is a promising stroma‐rich solid tumors’ treatment in the clinic.

Essential Hypertension (EH) results in the burden of cardiovascular disease (CVD) such as Heart Failure (HF) and Ischemic Stroke (IS). A rapidly emerging field involving the role of Wnt/β-catenin signaling pathway in cardiovascular development and dysfunction has recently drawn extensive attention. In the present study, we conducted a genetic association between genomic variants in Wnt/β-catenin signaling pathway and EH, HF, IS. A total of 95 SNPs in 12 Wnt signaling genes (WNT3A, WNT3, WNT4, DKK1, DKK2, LRP5, LRP6, CTNNB1, APC, FZD1, FRZB, SFRP1) were genotyped in 1,860 participants (440 patients with EH, 535 patients with HF, 421 patients with IS and 464 normal control subjects) using Sequenom MassArray technology. WNT3A rs752107(C > T) was strongly associated with an increased risk of EH, HF and IS. Compared with WNT3A rs752107 CC genotype, the CT genotype carriers had a 48% increased risk of EH (OR = 1.48, 95% CI = 1.12–1.96, P = 0.006), the TT genotype conferred a 139% increased risk of EH (OR = 2.39, 95% CI = 1.32–4.34, P = 0.003). Regarding HF and IS, the risk of HF in the T allele carriers (CT + TT) was nearly increased by 58% (OR = 1.58, 95% CI = 1.22–2.04, P = 4.40 × 10−4) and the risk of IS was increased by 37% (OR = 1.37, 95% CI = 1.04–1.79, P = 0.025). Expression quantitative trait loci (eQTL) analysis indicated that rs752107 C allele corresponded to a significant reduction of WNT3A expression. We described a genetic variant of WNT3A rs752107 in Wnt/β-catenin signaling strongly associated with the risk of EH, HF and IS for the first time.

Summary: Background: Portal hypertension (PH), which is closely associated with the severity of liver cirrhosis, has been suggested as a contraindication of liver resection for hepatocellular carcinoma (HCC). We aimed to explore the role of a potential player, histologic severity of liver cirrhosis, in affecting surgical outcomes of the patients with both HCC and PH. Methods: A total of 374 HCC patients with PH underwent resection for HCC were retrospectively reviewed. By using the Laennec staging system, the patients were divided into two groups: the mild-moderate cirrhosis (MMC) group and the severe cirrhosis (SC) group. Propensity score matching (PSM) was conducted at a 1:1 ratio between the two groups, and 89 patients were matched for each group. Short-term and long-term outcomes were compared between two groups before and after PSM. Results: The overall morbidity and 30-days mortality were significantly higher in the SC group than the MCC group (52.9% vs. 30.1%, P

Summary: Background/Objective: Previous studies have proposed several objective means for liver function assessment in hepatocellular carcinoma (HCC) patients; however, their efficiency in predicting survival of HCC rupture is unknown. Our study aims to confirm which is a better liver function model for ruptured HCC. Methods: A total of 230 patients with HCC ruptures at our center were included. Kaplan–Meier and Cox regression analyses were performed to compare long-term survival and short-term mortality. The 90-day mortality was compared with the area under the receiver characteristic curve. Logistic regression was used to determine the risk factors for 90-day deaths, and the discriminant ability of the model was measured. Results: There were significant differences in predicting OS of the Child-Pugh (CP) score in all patients, the non-surgical subgroup, and the surgical subgroup (all P

Abstract Background Gliomas are the most common primary tumors in central nervous system. Despite advances in diagnosis and therapy, the prognosis of glioma remains gloomy. Autophagy is a cellular catabolic process that degrades proteins and damaged organelles, which is implicated in tumorigenesis and tumor progression. Autophagy related 4C cysteine peptidase (ATG4C) is an autophagy regulator responsible for cleaving of pro-LC3 and delipidation of LC3 II. This study was designed to investigate the role of ATG4C in glioma progression and temozolomide (TMZ) chemosensitivity. Methods The association between ATG4C mRNA expression and prognosis of gliomas patients was analyzed using the TCGA datasets. The role of ATG4C in proliferation, apoptosis, autophagy, and TMZ chemosensitivity were investigated by silencing ATG4C in vivo. Ectopic xenograft nude mice model was established to investigate the effects of ATG4C on glioma growth in vivo. Results The median overall survival (OS) time of patients with higher ATG4C expression was significantly reduced (HR: 1.48, p = 9.91 × 10− 7). ATG4C mRNA expression was evidently increased with the rising of glioma grade (p = 2.97 × 10− 8). Knockdown ATG4C suppressed glioma cells proliferation by inducing cell cycle arrest at G1 phase. ATG4C depletion suppressed autophagy and triggered apoptosis through ROS accumulation. Depletion of ATG4C suppressed TMZ-activated autophagy and promoted sensitivity of glioma cells to TMZ. Additionally, ATG4C knockdown suppressed the growth of glioma remarkably in nude mice. Conclusion ATG4C is a potential prognostic predictor for glioma patient. Targeting ATG4C may provide promising therapy strategies for gliomas treatment.

Abstract Background The influence of DNMT3A R882 mutations on adult acute myeloid leukemia (AML) prognosis is still controversial presently. The influence of R882 allele ratio on drug response and prognosis of AML is unknown yet. Besides, it is obscure whether anthracyclines are involved in chemoresistance resulted from R882 mutations. Methods DNMT3A R882 mutations in 870 adult AML patients receiving standard induction therapy were detected by pyrosequencing. Associations of the mutants with responses to induction therapy and disease prognosis were analyzed. Results DNMT3A R882 mutations were detected in 74 (8.51%) patients and allele ratio of the mutations ranged from 6 to 50% in the cohort. After the first and second courses of induction therapy including aclarubicin, complete remission rates were significantly lower in carriers of the DNMT3A R882 mutants as compared with R882 wildtype patients (P = 0.022 and P = 0.038, respectively). Compared with R882 wild-type patients, those with the R882 mutations showed significantly shorter overall survival (OS) and disease-free survival (DFS) (P = 1.92 × 10−4 and P = 0.004, respectively). Patients with higher allele ratio of R882 mutations showed a significantly shorter OS as compared with the lower allele ratio group (P = 0.035). Conclusion Our results indicate that the impact of DNMT3A R882 mutations on AML prognosis was determined by the mutant-allele ratio and higher allele ratio could predict a worse prognosis, which might improve AML risk stratification. In addition, DNMT3A R882 mutations were associated with an inferior response to induction therapy with aclarubicin in Chinese AML patients.

Abstract Background & Aims Although the prognosis of patients with occult hepatitis B virus (HBV) infection (OBI) is usually benign, a small portion may undergo cirrhosis and subsequently hepatocellular carcinoma (HCC). We studied the mechanism of life-long Integration of virus DNA into OBI host’s genome, of which may induce hepatocyte transformation. Methods We applied HBV capture sequencing on single cells from an OBI patient who, developed multiple HCC tumors and underwent liver resection in May 2013 at Tongji Hospital in China. Despite with the undetectable virus DNA in serum, we determined the pattern of viral integration in tumor cells and adjacent non-tumor cells and obtained the details of the viral arrangement in host genome, and furthermore the HBV integrated region in cancer genome. Results HBV captured sequencing of tissues and individual cells revealed that samples from multiple tumors shared two viral integration sites that could affect three host genes, including CSMD2 on chr1 and MED30/EXT1 on chr8. Whole genome sequencing further indicated one hybrid chromosome formed by HBV integrations between chr1 and chr8 that was shared by multiple tumors. Additional 50 poorly differentiated liver tumors and the paired adjacent non-tumors were evaluated and functional studies suggested up-regulated EXT1 expression promoted HCC growth. We further observed that the most somatic mutations within the tumor cell genome were common among the multiple tumors, suggesting that HBV associated, multifocal HCC is monoclonal in origin. Conclusion Through analyzing the HBV integration sites in multifocal HCC, our data suggested that the tumor cells were monoclonal in origin and formed in the absence of active viral replication, whereas the affected host genes may subsequently contribute to carcinogenesis.

Abstract Background Previous studies reported that low level of oestradiol (E2) was associated with higher risk of cardiovascular disease (CVD). However, little study examined the relationship between E2 and CVD in longevous women, which were deficient in serum E2 for the post-menopausal status. Therefore, this study aims to explore the association between E2 and CVD risk factors in a group of female centenarians of Hainan, China. Methods A total of 413 female centenarians (aged from 100 to 115) from China Hainan Centenarian Cohort Study (CHCCS) were enrolled in this study. Home interviews were conducted to collected data on demographic characteristics, health-related lifestyles, and anthropometrics. The level of serum E2 was assessed in the Clinical Laboratory of Hainan branch of PLA General Hospital. The variables of CVD risk factors, including blood pressures, lipids and blood glucose, were measured through standard procedures. Results Significant negative correlations between levels of serum E2 and TC, HDL-C, and LDL-C were observed in this study. Compared with the highest group of E2, the odds ratio and 95% confidence intervals of high LDL-C in groups 3, 2 and 1 were OR1.94 (CI0.82–4.62), OR3.61 (CI1.27–10.25) and OR9.29 (CI2.08–41.53), respectively. Similarly, the prevalence of hypertension was decreased with the increase of serum E2. The odds ratio and 95% confidence intervals of stage-2 hypertension in groups 3, 2 and 1 versus highest E2 group were OR1.34 (CI0.49–3.72), OR1.36 (CI0.47–3.99) and OR1.38 (CI0.45–4.20), respectively. Conclusions This study examined the relationship between E2 and CVD risk factors in a group of community-based female centenarians. A negative correlations between serum E2 levels and CVD risk factors, i.e. high level of LDL-C, TC, and hypertension were observed in this population. Besides, the level of serum E2 is also negatively correlated with HDL-C. Further studies on the correlation between serum E2 and CVD risk factors, especially dyslipidemia, in longevous and post-menopausal women are warranted.

Fam134b (JK‐1, RETREG1) was first identified as an oncogene in esophageal squamous cell carcinoma. However, the roles of FAM134B during tumorigenesis of hepatocellular carcinoma (HCC) and in epithelial‐to‐mesenchymal transition (EMT) were previously unclear. In this study, we investigated the function of FAM134B in HCC and the related tumorigenesis mechanisms, as well as how FAM134B induces EMT. We detected the expression of FAM134B in a normal hepatic cell line, HCC cell lines, fresh specimens, and a HCC tissue microarray. A retrospective study of 122 paired HCC tissue microarrays was used to analyze the correlation between FAM134B and clinical features. Gain‐ and loss‐of‐function experiments, rescue experiments, Akt pathway activator/inhibitors, nude mice xenograft models, and nude mice lung metastasis models were used to determine the underlying mechanisms of FAM134B in inducing tumorigenesis and EMT in vitro and in vivo. The expression level of FAM134B was highly elevated in HCC, as compared with that in normal liver tissues and normal hepatic cells. Overexpression of FAM134B was significantly associated with tumor size (P = 0.025), pathological vascular invasion (P = 0.026), differentiation grade (P = 0.023), cancer recurrence (P = 0.044), and portal vein tumor thrombus (P = 0.036) in HCC. Patients with high expression of FAM134B had shorter overall survival and disease‐free survival than patients with non‐high expression of FAM134B. Furthermore, knockdown of FAM134B with shRNAs inhibited cell growth and motility, as well as tumor formation and metastasis in nude mice, all of which were promoted by overexpression of FAM134B. Our study demonstrated that Fam134b is an oncogene that plays a crucial role in HCC via the Akt signaling pathway with subsequent glycogen synthase kinase‐3β phosphorylation, accumulation of β‐catenin, and stabilization of Snail, which promotes tumorigenesis, EMT, and tumor metastasis in HCC.

Olfactory ensheathing cells from the olfactory bulb and olfactory mucosa have been found to increase axonal sprouting and pathfinding and promote the recovery of vibrissae motor performance in facial nerve transection injured rats. However, it is not yet clear whether olfactory ensheathing cells promote the reparation of facial nerve defects in rats. In this study, a collagen sponge and silicone tube neural conduit was implanted into the 6-mm defect of the buccal branch of the facial nerve in adult rats. Olfactory ensheathing cells isolated from the olfactory bulb of newborn Sprague-Dawley rats were injected into the neural conduits connecting the ends of the broken nerves, the morphology and function of the regenerated nerves were compared between the rats implanted with olfactory ensheathing cells with the rats injected with saline. Facial paralysis was assessed. Nerve electrography was used to measure facial nerve-induced action potentials. Visual inspection, anatomical microscopy and hematoxylin-eosin staining were used to assess the histomorphology around the transplanted neural conduit and the morphology of the regenerated nerve. Using fluorogold retrograde tracing, toluidine blue staining and lead uranyl acetate staining, we also measured the number of neurons in the anterior exterior lateral facial nerve motor nucleus, the number of myelinated nerve fibers, and nerve fiber diameter and myelin sheath thickness, respectively. After surgery, olfactory ensheathing cells decreased facial paralysis and the latency of the facial nerve-induced action potentials. There were no differences in the general morphology of the regenerating nerves between the rats implanted with olfactory ensheathing cells and the rats injected with saline. Between-group results showed that olfactory ensheathing cell treatment increased the number of regenerated neurons, improved nerve fiber morphology, and increased the number of myelinated nerve fibers, nerve fiber diameter, and myelin sheath thickness. In conclusion, implantation of olfactory ensheathing cells can promote regeneration and functional recovery after facial nerve damage in rats.

Background. The CXC chemokines belong to a unique family of cytokines that participates in the progression and development of many malignant tumors. Evidence for the relationship between chemokine (C-X-C motif) receptor 2 (CXCR2) C1208T polymorphism and susceptibility to cancer remains inconsistent. Methods. Odds ratios (ORs), 95% confidence intervals (CIs), and combined analysis were used to investigate the effect of CXCR2 variation on cancer risk. Gene Set Enrichment Analysis (GSEA) and enzyme-linked immunosorbent assay (ELISA) were also used to evaluate the expression of CXCR2 in prostate cancer (PCA). Results. Across 11 case-control studies, 4,909 cases and 5,884 controls were involved in the current analysis. Individuals with a TT genotype were associated with increased risk of digestive cancer, compared to those with a TC+CC genotype (OR=1.16, 95%CI=1.02-1.31, P=0.025). Individuals carrying the TT genotype had a 39% higher risk of urinary cancer than those carrying CC genotype (OR=1.39, 95%CI=1.04-1.87, P=0.025). Individuals with a TT genotype showed a 56% augmented breast cancer risk, compared to those with a CC genotype (OR=1.56, 95%CI=1.03-2.35, P=0.034). It was found that CXCR2 expression was downregulated in PCA. Compared with PCA subjects carrying the CC genotype, the expression of CXCR2 was decreased in patients with the TT genotype. Conclusions. The CXCR2 C1208T variation was associated with elevated risk of urinary, breast, and digestive cancer. However, the C1208T polymorphism was correlated with attenuated risk of lung cancer.