A prognostic model for predicting progression-free survival in patients with advanced non-small cell lung cancer after image-guided microwave ablation plus chemotherapy.

OBJECTIVES: This study aimed to build and validate a prediction model that can predict progression-free survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC) after image-guided microwave ablation (MWA) plus chemotherapy. METHODS: Data from a previous multi-center randomized controlled trial (RCT) was used and assigned to either the training data set or the external validation data set according to the location of the centers. Potential prognostic factors were identified by multivariable analysis in the training data set and used to construct a nomogram. After bootstraps internal and external validation, the predictive performance was evaluated by concordance index (C-index), Brier Score, and calibration curves. Risk group stratification was conducted using the score calculated by the nomogram. Then a simplified scoring system was built to make risk group stratification more convenient. RESULTS: In total, 148 patients (training data set: n = 112; external validation data set: n = 36) were enrolled for analysis. Six potential predictors were identified and entered into the nomogram, including weight loss, histology, clinical TNM stage, clinical N category, tumor location, and tumor size. The C-indexes were 0.77 (95% CI, 0.65-0.88, internal validation) and 0.64 (95% CI, 0.43-0.85, external validation). The survival curves of different risk groups also displayed significant distinction (p < 0.0001). CONCLUSIONS: We found weight loss, histology, clinical TNM stage, clinical N category, tumor location, and tumor size were prognostic factors of progression after receiving MWA plus chemotherapy and constructed a prediction model that can predict PFS. CLINICAL RELEVANCE STATEMENT: The nomogram and scoring system will assist physicians to predict the individualized PFS of their patients and decide whether to perform or terminate MWA and chemotherapy according to the expected benefits. KEY POINTS: • Build and validate a prognostic model using the data from a previous randomized controlled trial to predict progression-free survival after receiving MWA plus chemotherapy. • Weight loss, histology, clinical TNM stage, clinical N category, tumor location, and tumor size were prognostic factors. • The nomogram and scoring system published by the prediction model can be used to assist physicians to make clinical decisions.

Interaction between Changan Granule and its main components in the plasma and CYP450 enzymes.

ETHNOPHARMACOLOGICAL RELEVANCE: Changan Granule (CAG) is a Chinese patent drug developed based on an empirical prescription in accordance with the formulation theory of Traditional Chinese Medicine. The prescription is composed of eight herbal drugs which have been traditionally used by Chinese people for a long history. It has effects of invigorating spleen and supplementing qi, as well as regulating liver and ceasing diarrhea, and is indicated for the treatment of irritable bowel syndrome (IBS). AIM OF THE STUDY: This study was aimed to investigate the interaction between CAG and its main components and cytochrome P450 (CYP450) enzymes so as to characterize the major metabolites and metabolic enzymes and evaluate the safety concerns to its clinical use. MATERIALS AND METHODS: Both in vivo and in vitro experiments using such as diarrhea-predominant IBS (IBS-D) rat model, HepG2 cells, and human liver microsomes (HLM) were carried out to investigate the interaction between CAG and its main components and CYP450 enzymes. Real-time quantitative PCR (qPCR), ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and cocktail probes were employed to qualitatively or quantitatively measure the metabolites and metabolic enzymes. RESULTS: CAG inhibited the enzyme activities of CYP1A2, CYP2E1, CYP2D6, CYP2C9, and CYP3A4 and the mRNA expressions of CYP2E1, CYP2C9, CYP3A4, and CYP2D6 in vitro. CAG down-regulated the increased expression of CYP1A2 and up-regulated the decreased expression of CYP3A1 in vivo. Twenty-two metabolites were characterized from the main components of CAG after incubation with HLM in vitro. CYP2D6, CYP2E1, CYP3A4 and CYP2C9 were identified as the characteristic metabolic enzymes. CONCLUSIONS: This study provides a reference for clinical application of CAG in safety. CAG and CYP450 enzymes are interacted. CAG is mainly metabolized by CYP2E1 and CYP2D6. The expression of CYP2E1 and CYP2D6 are more susceptible to be influenced by CAG in comparison with that of CYP3A4, CYP2C9 and CYP1A2. It implies the potential risk of interaction when CAG is taken together with the drugs metabolized by CYP2E1 and CYP2D6.

Synergistic Antibacterial Effect and Mechanism of Allicin and an Enterobacter cloacae Bacteriophage.

Enterobacter cloacae is a troublesome pathogen causing refractory infections of the lower respiratory tract, urethra and abdominal cavity, endocarditis, osteomyelitis, and neonatal septicemia. It is prone to developing resistance to ordinary antibiotics and has brought a serious problem to clinical treatment. An artful synergistic combination of an antibacterial natural product allicin and a newly isolated bacteriophage, named BD523, was constructed herein. This combination significantly lowered effective dosage of allicin and effectually overcame bacterial drug-resistance. We experimentally evidenced that allicin interacts with bacterial DNA in the groove region by inserting itself into the DNA double helix and, subsequently, disrupts the bacterial DNA by cleaving phosphate diester bonds of deoxynucleotides. Further, BD523 destroys the cell wall and membrane of bacteria by synthesizing lyase proteins, including holin and endolysins. Thus, the synergistic effect of the combination benefits from complementary targeting mechanisms of allicin and BD523. They cooperatively act on bacterial DNA, cell wall, and membrane to improve antibacterial efficiency and avoid drug-resistance. IMPORTANCE Bacterial drug-resistance is a serious problem afflicting pharmacologists all over the world. Many strategies have been developed and practiced to overcome it, but almost no one is satisfactory due to the continual change of bacteria. Combinations of antibiotics and bacteriophages are promising because of the cooperation of 2 bacterial killers with distinct mechanisms. The combination of allicin and an Enterobacter cloacae bacteriophage reported herein can significantly improve the effect of allicin against E. cloacae. Its synergistic effect was even superior to the combination of bacteriophage and neomycin, of which the MIC was significantly lower than allicin. It was ascribed to the complementary antibacterial and the possible resistance-proof mechanism of bacteriophage and allicin. This study provided a pragmatic way to conquer the cunning bacterium, and may offer reference for research and development of new bacterial killers.

Electroacupuncture in promoting neural repair after spinal cord injury: Inhibiting the Notch signaling pathway and regulating downstream proteins expression.

Spinal cord injury (SCI) is one of the serious central nervous system injuries and the incidence of SCI continues to increase. Previous studies have indicated that electroacupuncture (EA) is beneficial for promoting recovery after SCI. In the present study, we attempted to evaluate how EA can promote the neural repair in SCI model rats by observing changes in the Notch signaling pathway. Experimental rats were randomly divided into four groups. Each group had its own intervention period: 1 day, 7 days, 14 days, and 28 days, and five randomized subgroups: blank control (B) group, blank electroacupuncture (BE) group, sham operation (S) group, model control (M) group and EA group. Animals in the EA group and the BE group were treated with EA at Dazhui (GV14) and Mingmen (GV4) acupoints for 20 min. After the intervention period, the Basso-Beattie-Bresnahan (BBB) score was used to evaluate the neurological function. We found that BBB score increased in EA-treated groups. Hematoxylin and eosin staining was used to observe pathological changes in the injured spinal cord and the results showed that EA therapy could promote the repair of injured spinal cord tissue. Immunohistochemistry and Western blot methods were used to detect the expression of proteins Delta1, Presenilin1, Hes1, and Hes5 in the injured spinal cord. The results showed that the expression levels of Delta1, Presenilin1, Hes1, and Hes5 increased significantly after SCI and decreased after EA treatment. Our study suggested that the possible mechanism by which EA could benefit the recovery after SCI in rats may include inhibiting the Notch signaling pathway and regulating the downstream proteins expression. In addition, our study can provide reference for selecting acupoints and treatment cycle in the treatment of SCI.

Psychological impact of COVID-19 pandemic on healthcare workers in China Xi'an central hospital.

OBJECTIVE: COVID-19 significantly altered our routine, lifestyle, and stress level across the globe. This study investigated the psychological impact of COVID-19 on healthcare workers in China Xi'an Center hospital. METHODS: A modified online questionnaire of Psychological Status and the General Health Questionnaire (GHQ-12) was provided to 1,967 healthcare workers during the COVID-19 pandemic. Participation was voluntary, and the responses were anonymous. The survey lasted for 2 weeks, and the GHQ-12 was completed every other day. The data were collected automatically and electronically and then statistically analyzed. RESULTS: The 431 (21.9%) responders included 214 nurses (49.7%), 146 clinicians (33.9%), 29 pharmacists (6.7%), 15 medical technicians (3.5%), 17 administrative staff (3.9%), and 10 other departments (2.3%). Of these, 46.2% had 10 years of work experiences or more and 78.2% were married. Work experience increased emotional stress as 23% of participants with 10 years or more of experience exhibited higher stress compared to those with fewer than 3 years of work experience (7.5%). Moreover, 33.3% of participants who worked in or were exposed to the affected areas of the pandemic experienced psychological stress. Overall, this study identified four factors that were significantly associated with psychological stress: (a) work experience (OR 2.99; 95% CI: 1.06 to 8.41); (b) change in job position (OR 1.99; 95% CI: 1.10 to 3.59); (c) change in lifestyle (OR 4.06; 95% CI: 1.81 to 9.10); and (d) need for psychological counseling (OR 3.07; 95% CI: 1.62 to 5.82). CONCLUSIONS: The COVID-19 pandemic has increased psychological stress among healthcare workers with 10 years or more work experiences and who recently experienced a career position change.

Intestinal bacteria are involved in Radix Glycyrrhizae and Radix Euphorbiae Pekinensis incompatibility.

ETHNOPHARMACOLOGICAL RELEVANCE: Eighteen Incompatible Medicaments (EIM) belongs to the category of incompatibility of Traditional Chinese medicine (TCM). This theory forbids concomitant using any one of the eighteen herbal pairs such as Radix Glycyrrhizae (RG)-Radix Euphorbiae Pekinensis (REP), Radix Aconiti-Bulbus Fritiliariae Cirrhosae, and Radix et Rhizoma Veratri Nigri-Radix Ginseng. Concomitant using RG and REP could result in more serious adverse effects on major organs such as kidney, heart, and liver. AIM OF THE STUDY: To investigate the effects of RG-REP decoctions on gut microbiota and short-chain fatty acids (SCFAs) for the purpose of elucidating the mechanism of RG-REP incompatibility. MATERIALS AND METHODS: Six groups of male SD rats were intragastrically administrated with distilled water, RG decoction, REP decoction, 1:1 RG-REP decoction, 2:1 RG-REP decoction and 3:1 RG-REP decoction, respectively, twice daily for 30 consecutive days, and the feces of each rat was separately sampled for gut microbiota analysis and SCFAs assay. 16S rDNA sequencing was employed to comparatively investigate the structure and abundance of intestinal bacteria in rat feces. Gas chromatography (GC) was used to quantitatively determine the contents of SCFAs in rat feces and in vitro samples. The correlation between bacteria and the production of SCFAs was analyzed by Spearman correlation analysis. An in vitro model of human intestinal bacteria was also constructed to simulate and validate the in vivo experiment. RESULTS: The contents of butyric acid in both rat feces and in vitro samples decreased in RG-REP groups. The general structure of gut microbiota in RG-REP groups was not significantly different from that in control group. However, RG alone increased the abundance of Lactobacillus while this effect was counteracted by concomitant using with REP. REP alone decreased the abundance of two interrelated species, Akkermansia and Butyricimonas, and this effect was strengthened by concomitant using REP with RG in the ratio of 1:1. In comparison with REP alone, RG-REP combination also significantly increased the abundance of Streptococcus and Prevotella. CONCLUSION: The incompatibility of RG-REP combination is associated with its negative effect against probiotic bacteria and positive effect on conditional pathogenic bacteria as well as its inhibition on butyric acid production.

The role of triage in the prevention and control of COVID-19.

OBJECTIVE: To prevent and control public health emergencies, we set up a prescreening and triage workflow and analyzed the effects on coronavirus disease 2019 (COVID-19). METHODS: In accordance with the requirements of the level 1 emergency response of public health emergencies in Shaanxi Province, China, a triage process for COVID-19 was established to guide patients through a 4-level triage process during their hospital visits. The diagnosis of COVID-19 was based on positive COVID-19 nucleic acid testing according to the unified triage standards of the Guidelines for the Diagnosis and Treatment of Novel Coronavirus Pneumonia (Trial version 4),4 issued by the National Health Commission of the People's Republic of China. RESULTS: The screened rate of suspected COVID-19 was 1.63% (4 of 246) in the general fever outpatient clinic and 8.28% (13 of 157) in the COVID-19 outpatient clinic, and they showed a significant difference (P = .00). CONCLUSIONS: The triage procedure effectively screened the patients and identified the high-risk population.

Sporadic human cutaneous anthrax outbreak in Shaanxi Province, China: report of two cases from 2018

ABSTRACT China's compulsory annual livestock anthrax vaccination policy has remarkably reduced but not completely eradicated human anthrax infections. Herein we describe a sporadic human cutaneous anthrax outbreak involving two cases in 2018 in Shaanxi Province, both involving herdsman who dealt with unvaccinated and potentially sick cattle. Both patients showed Bacillus anthracis-positive blister smear and blood culture. Treatment with penicillin was followed by uneventful recovery for both. The prompt performance of the prophylactic measures successfully interrupted the further transmission of this sporadic human cutaneous anthrax outbreak.

Sporadic human cutaneous anthrax outbreak in Shaanxi Province, China: report of two cases from 2018.

China's compulsory annual livestock anthrax vaccination policy has remarkably reduced but not completely eradicated human anthrax infections. Herein we describe a sporadic human cutaneous anthrax outbreak involving two cases in 2018 in Shaanxi Province, both involving herdsman who dealt with unvaccinated and potentially sick cattle. Both patients showed Bacillus anthracis-positive blister smear and blood culture. Treatment with penicillin was followed by uneventful recovery for both. The prompt performance of the prophylactic measures successfully interrupted the further transmission of this sporadic human cutaneous anthrax outbreak.

Microwave ablation followed by immediate biopsy in the treatment of non-small cell lung cancer.

BACKGROUND: To evaluate the efficacy and safety of microwave ablation (MWA) followed by immediate biopsy in the treatment of non-small cell lung cancer (NSCLC) and to clarify whether pathology changes can predict treatment responses and patient survival. METHODS: Patients with pathologically confirmed NSCLC pre-ablation were treated with MWA, and immediate biopsy was carried out right after ablation in one procedure. Pathology changes were categorized according to the pre- and postablation pathology: Group A, same histology type; Group B, paired histology type with burning degeneration; Group C, no definite histology type; Group D, no definite cancer cells. The internal correlations between pathology changes and baseline characteristics, responses to MWA and survival were evaluated. RESULTS: A total of 68 patients were enrolled in the study, of which 19, 28, 11 and 10 patients were classified into Group A, Group B, Group C and Group D, respectively. In total, 85.3 and 69.1% patients were diagnosed with malignant tumors and the same pathology type, respectively. No significant difference in clinical-pathologic characteristics or response to MWA between the groups was observed. Upon combining Groups A, B and C, Group D exhibited longer progression-free survival (PFS) (Groups A + B + C versus Group D, 11.7 months, 95% CI 9.6-13.7 versus 26.6 months, 95% CI 19.0-34.2, p = .253) and overall survival (OS) (15.9 months, 95% CI 14.2-17.5, versus 29.8 months, 95% CI, 24.3-35.3, p = .395), although no significant differences were observed. Complications were identified in 63 (92.6%), of which 17 (25.0%) patients had major complications. CONCLUSIONS: Immediate biopsy post-MWA can distinguish cancer cells or histology types in most cases of NSCLC. However, pathology changes pre- and postablation could not predict the response to MWA and patient survival.

Alpha-Fetoprotein and Hepatocellular Carcinoma Immunity.

Hepatocarcinoma is one of the most prevalent gastroenterological cancers in the world with less effective therapy. As an oncofetal antigen and diagnostic marker for liver cancer, alpha-fetoprotein (AFP) possesses a variety of biological functions. Except for its diagnosis in liver cancer, AFP has become a target for liver cancer immunotherapy. Although the immunogenicity of AFP is weak and it could induce the immune escapes through inhibiting the function of dendritic cells, natural killer cells, and T lymphocytes, AFP has attracted more attention in liver cancer immunotherapy. By in vitro modification, the immunogenicity and immune response of AFP could be enhanced. AFP-modified immune cell vaccine or peptide vaccine has displayed the specific antitumor immunity against AFP-positive tumor cells and laid a better foundation for the immunotherapy of liver cancer.

Mast cells are important regulator of acupoint sensitization via the secretion of tryptase, 5-hydroxytryptamine, and histamine.

Mast cells (MCs) play a crucial role in mediating the establishment of networks among the circulatory, nervous and immune system at acupoints. However, the changes which occur in MCs during acupoint sensitization, i.e. the dynamic transformation of an acupoint from a "silenced" to an "activated" status, remain uncharacterized. To investigate the morphological and functional changes of MCs as an aid to understanding the cellular mechanism underlying acupoint sensitization, a rat model of knee osteoarthritis (OA) was induced by an injection of mono-iodoacetate (MIA) on day 0. On day 14, toluidine blue and immunofluorescence staining were used to observe the recruitment and degranulation of MCs and the release of mast cell co-expressed mediators: tryptase, 5-hydroxytryptamine (5-HT) and histamine (HA) at the acupoints Yanglingquan (GB34), Heding (EX-LE2) and Weizhong (BL40). Results showed that the number of MCs as well as the percentages of degranulated and extensively degranulated MCs at the acupoints GB34 and EX-LE2 in the light (A), mild (B), heavy (C) osteoarthritis groups were larger than those in the normal control (N) and normal saline (NS) groups (p < 0.01). Comparisons among the A, B and C groups suggested that the number and the degranulation extent of the MCs at the acupoints GB34 and EX-LE2 were positively correlated with the severity of the disease. Some MCs in the A, B and C group showed the release of 5-HT, HA, and tryptase in degranulation at the acupoints GB34 and EX-LE2. Such changes in MCs were not observed at the acupoint BL40. In conclusion, this study confirmed that acupoint sensitization is associated with the increase in recruitment and degranulation levels of MCs on a acupoint-specific and disease severity-dependent manner. The release of tryptase, 5-HT, and HA during MC degranulation is likely to be one of the cellular mechanisms occurring during acupoint sensitization.

[Prospects of the Application of Photoacoustic Technique in Microcirculation Imaging Research on the Acupoints Sensitization].

Research on the imaging of acupoint sensitization is inadequate, especially at the microcirculation level. Photoacoustic imaging is one of the main techniques used in microcirculation imaging, and has the characteristics of high contrast, high detection depth and high sensitivity for tissue function. In the present paper the authors briefly introduce photoacoustic imaging and review research advances in photoacoustic imaging of microcirculation from the aspects of structure and function. The photoacoustic technique can three-dimensionally image and quantitatively examine microcirculation structure to the depth of interest tissues with high spatial resolution, and can dynamically measure total hemoglobin concentration and its oxygenation level, blood flow velocity, oxygen metabolism level, vasoconstriction, vasodilation, and hemodynamics of a target vessel in real time. Based on these factors, the prospects of the application of photoacoustic imaging are debated. The authors propose that photoacoustic imaging is appropriate for research on the sensitization of microcirculation in acupoints and can be applied to sensitized acupoints locally or in the brain, which is expected to further determine characteristic changes in the microcirculation of sensitized acupoints and enrich the specific connotation of the central sensitization of acupoints.

Anti-tumor bioactivities of curcumin on mice loaded with gastric carcinoma.

Curcumin, a derivative from the dried rhizome of curcuma longa, has been proven to possess anti-tumor effects. However, the detailed molecular mechanisms have not been fully elucidated. In this study, we aimed to explore the anti-tumor mechanisms of curcumin in treating gastric cancer. BALB/C mice grafted with a mouse gastric adenocarcinoma cell line (MFC) were used as the experimental model. Mice received different doses of curcumin after grafting. Tumor size was measured and tumor weight was determined after tumor inoculation. TUNEL assay and flow cytometric analysis were applied to evaluate the apoptosis of the cancer cells. Serum cytokines IFN-γ, TNF-α, granzyme B and perforin were detected by ELISA assay. The anti-tumor effect was determined using cytotoxic T-lymphocyte (CTL) assays and in vivo tumor prevention tests. The expression of DEC1, HIF-1α, STAT3 and VEGF in tumor tissues was examined by immunostaining and analyzed using an Image J analysis system. Compared with controls, tumor growth (size and weight) was significantly inhibited by curcumin treatment (P < 0.05). The apoptotic index in gastric cancer cells was significantly increased in the curcumin treatment group. Splenocyte cells from mice treated with curcumin exhibited higher cytolytic effects on MFC cancer cells than those from mice treated with saline (P < 0.01). The expression of DEC1, HIF-1α, STAT3 and VEGF in tumor tissues was down-regulated after curcumin treatment. Our results indicate that curcumin inhibits the proliferation of gastric carcinoma by inducing the apoptosis of tumor cells, activating immune cells to secrete a large amount of cytokines, and down-regulating the DEC1, HIF-1α, VEGF and STAT3 signal transduction pathways.

Incidence and risk of infections associated with EGFR-TKIs in advanced non-small-cell lung cancer: a systematic review and meta-analysis of randomized controlled trials.

Currently, the overall incidence and risk of infections with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients remained undetermined. We searched Pubmed for related articles published from 1 January 1990 to 31 November 2015. Eligible studies included prospective randomized controlled trials (RCTs) evaluating therapy with or without EGFR-TKIs in patients with NSCLC. Data on infections were extracted. Pooled incidence, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were calculated. A total of 17,420 patients from 25 RCTs were included. The use of EGFR-TKIs significantly increased the risk of developing all-grade infections (Peto OR 1.48, 95%CI: 1.12-1.96, p = 0.006) in NSCLC patients, but not for severe (Peto OR 1.26, 95%CI: 0.96-1.67, p = 0.098) and fatal infections (Peto OR 0.81, 95%CI: 0.43-1.53, p = 0.52). Meta-regression indicated the risk of infections tended to increase with the treatment duration of EGFR-TKIs. No publication of bias was detected. In conclusion, the use of EGFR-TKIs significantly increased the risk of developing all-grade infectious events in NSCLC patients, but not for severe and fatal infections. Clinicians should be aware of the risks of infections with the administration of these drugs in these patients.

Recombinant heat shock protein 70 functional peptide and alpha-fetoprotein epitope peptide vaccine elicits specific anti-tumor immunity.

Alpha-fetoprotein (AFP) is a marker of hepatocellular carcinoma (HCC) and serves as a target for immunotherapy. However, current treatments targeting AFP are not reproducible and do not provide complete protection against cancer. This issue may be solved by developing novel therapeutic vaccines with enhanced immunogenicity that could effectively target AFP-expressing tumors. In this study, we report construction of a therapeutic peptide vaccine by linking heat shock protein 70 (HSP70) functional peptide to the AFP epitope to obtain HSP70-P/AFP-P. This novel peptide was administered into BALB/c mice to observe the effects. Quantification of AFP-specific CD8 + T cells that secrete IFN-γ in these mice via ELISPOT revealed the synergistic effects of HSP70-P/AFP-P with increased numbers of AFP-specific CD8 + T cells. Similarly, ELISA analysis showed increased granzyme B and perforin released by natural killer cells. Moreover, in vitro cytotoxic T-lymphocyte assays and in vivo tumor preventive experiments clearly showed the higher antitumor effects of HSP70-P/AFP-P against AFP-expressing tumors. These results show that treatment of BALB/c mice with HSP70-P/AFP-P induced stronger T-cells responses and improved protective immunity. Our data suggest that HSP70-P/AFP-P may be used as a therapeutic approach in the treatment of AFP-expressing cancers.

Novel rapid molecular diagnosis of fetal chromosomal abnormalities associated with recurrent pregnancy loss.

INTRODUCTION: Labor-intensive karyotyping is used as the reference standard diagnostic test to identify copy number variants (CNVs) in the fetal genome after recurrent pregnancy loss. Our aim was to present and evaluate a novel molecular assay called CNVplex that could potentially be used as an alternative method to conventional karyotyping for diagnosing fetal chromosomal abnormalities associated with recurrent pregnancy loss. MATERIAL AND METHODS: Using karyotyping as the reference standard, CNVplex was performed to identify fetal chromosomal abnormalities in the chorionic villus samples from 76 women experiencing at least two pregnancy losses. Its diagnostic accuracy, sensitivity, and specificity were evaluated to detect aneuploidies associated with recurrent pregnancy loss. Turnaround time and costs of CNVplex were also measured. RESULTS: Diagnostic accuracy of CNVplex in aneuploidies that are associated with recurrent pregnancy loss was 1.0 (95% CI 0.94-1.0), sensitivity was 100% (95% CI 0.89-1.0), and specificity was 100% (95% CI 0.875-1.0). Diagnostic accuracy of CNVplex was similar to that of karyotyping. Both karyotyping and CNVplex assay detected 27 autosomal trisomies, three 45,X monosomies, and three polyploidies. CNVplex also detected additional novel structural abnormalities of the fetal genome. Compared with karyotyping, CNVplex significantly (p = 0.001) reduced the waiting time by 13.98 days (95% CI 13.88-14.08) and the cost by US $241 (95% CI 234.53-247.47). CONCLUSIONS: CNVplex is a novel effective assay for diagnosing fetal chromosomal abnormalities associated with recurrent pregnancy loss. In the routine clinical work-up of recurrent pregnancy loss, diagnostic accuracy of CNVplex is comparable to that of conventional karyotyping but it requires less waiting time and has lower cost.

Glycoprotein 96 and α-fetoprotein cross-linking complexes elicited specific antitumor immunity.

Hepatocellular carcinoma (HCC) is one of the most common malignant gastroenterological cancers over the world. α-fetoprotein (AFP) is an oncofetal protein produced during HCC development that could generate weaker and less reproducible antitumor protection, and it may serve as a target for immunotherapy. Therefore, it is imperative to enhance its immunogenicity and develop therapeutic vaccines to eliminate AFP-expressing tumors. In this study, by way of glutaraldehyde cross-linking, we constructed a potential therapeutic protein vaccine, glycoprotein 96 (gp96)/AFP. Our results demonstrated that AFP and gp96 synergistically exhibited significant increase in AFP-specific CD8⁺ T-cell responses and impressive cytotoxic antitumor effect against AFP-expressing tumors. Priming mice with the reconstructed vaccine, we elicited robust strong protective immunity. Our study suggests that tumor vaccine by cross-linking tumor antigen and gp96 is a promising approach to cancer therapy.

HSP72 and gp96 in gastroenterological cancers.

Heat shock protein 72 (HSP72) and glycoprotein 96 (gp96) are highly expressed in cancer tissues. Recent studies indicate the possible roles of HSP72 and gp96 in the development and progression of gastrointestinal carcinomas but detailed mechanisms are still ambiguous. Human esophageal cancer, gastric cancer, colon cancer and liver cancer are common gastrointestinal malignant carcinomas in the world. The studies indicated that there existed a significant correlation between the expression of HSP72, gp96 and the development and progression of digestive carcinomas. HSP72 and gp96 expression were significantly associated with the presence of tumor infiltration, lymph node and remote metastasis. Interestingly, studies have found that HSP72 chaperoned alpha-fetoprotein (AFP), HBx in hepatocellular carcinoma, and CD44 in colonic carcinomas. The further researches demonstrated that HSP72-AFP or gp96-AFP recombined vaccine could elicit specific anti-tumor immunity. The high-level expression of HSP72 and gp96 may be not only used as diagnostic or prognostic markers for gastrointestinal carcinomas but also as better immunotherapeutic vaccines in the cancers.