Combined effects of cadmium and sulfamethoxazole on Eisenia fetida: Insights into accumulation, subcellular partitioning, biomarkers and toxicological responses.

Cadmium (Cd) and sulfamethoxazole (SMX) frequently coexist in farmlands, yet their synergistic toxicological impacts on terrestrial invertebrates remain unexplored. In this study, earthworms were exposed to artificial soils percolated with Cd (5 mg/kg), SMX (5 mg/kg) or combination of them for 7 days, followed by a 12-day elimination phase in uncontaminated soil. The uptake of Cd and SMX by the earthworms, along with their subcellular distribution, was meticulously analyzed. Additionally, a suite of biomarkers-including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and weight loss-were evaluated to assess the health status of the earthworms and the toxicological effects of the Cd and SMX mixture. Notably, the cotreatment with Cd and SMX resulted in a significantly higher weight loss in Eisenia fetida (41.25 %) compared to exposure to Cd alone (26.84 %). Moreover, the cotreatment group exhibited substantially higher concentrations of Cd in the total internal body, fraction C (cytosol), and fraction E (tissue fragments and cell membranes) in Eisenia fetida compared to Cd alone counterparts. The combined exposure also significantly elevated the SMX levels in the total body and fraction C compared with the SMX-only treated earthworms. Additionally, Eisenia fetida subjected to the combined treatment showed markedly increased activities of SOD, CAT, and MDA compared to those treated with Cd alone. The effect addition indices (EAIs), ranging from 1.00 to 2.23, unequivocally demonstrated a synergistic effect of the combined treatments. Interestingly, relocating the earthworms to clean soil did not mitigate the observed adverse effects. These findings underscore the increased risk posed by the Cd-SMX complex to terrestrial invertebrates in agricultural areas.

Yield and cost of government-organized colorectal cancer screening in young high-risk population in Northeast China.

Guidelines for colorectal cancer (CRC) screening recommend screening at age 40 for high-risk population in China. However, the yield and cost of CRC screening in younger population are lacking. This analysis aimed to evaluate the yield and cost of CRC screening in high-risk 40- to 54-year-olds. Individuals aged 40-54 years who were determined to have a high risk of CRC were recruited from December 2012 to December 2019. We calculated odds ratios (OR) and 95% confidence intervals (CI) for the detection rate of colorectal lesions among the three age groups and further calculated number of colonoscopies needed to screen (NNS) to detect one advanced lesion and cost of each group. The detection rates of advanced colorectal neoplasm in men aged 45-49 years (OR = 2.00, 95% CI: 0.93-4.30) and 50-54 years (OR = 2.19, 95% CI: 1.04-4.62) were higher than that aged 40-44 years. The detection rates of colorectal adenoma in women aged 50-54 years was higher than that aged 40-44 years (OR = 1.64, 95% CI: 1.23-2.19). Among the male screening population, NNS and cost to detect one advanced lesion in participants aged 45-49 years were similar to that aged 50-54 years, saving approximately half endoscopic resources and financial expenses compared with screening that aged 40-44 years. From the perspective of screening results and costs, it might be beneficial to delay the starting age of screening by gender. This study may provide reference for optimizing CRC screening strategies.

Skin sequelae in patients with infantile hemangioma: a systematic review.

Infantile hemangioma (IH) is the most common vascular tumor in infancy. Although IHs can regress spontaneously, some problematic IHs still need treatment. However, either treated or untreated IHs may leave skin sequelae which can cause permanent disfigurement. Many studies evaluated the short-term efficacy of different kinds of treatment, but now, few studies are focusing on long-term skin sequelae. The objectives of our systemic review were to identify skin sequelae of IH thoroughly, determine specific factors associated with long-term IH sequelae, and learn how to improve these sequelae. We searched the following electronic databases: PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov. Three independent authors assessed the articles, and we reported this systemic review following PRISMA guidelines. Of 4448 articles initially identified, 62 underwent full-text review, and 17 met inclusion criteria. The overall rate of sequelae ranged from 5.3 to 93.5%. Factors associated with skin sequelae included patients' demographics, hemangioma characteristics, and treatment factors. What is Known: • Infantile hemangioma is the most common vascular tumor during infancy. • Infantile hemangiomas can regress spontaneously but either treated or untreated patients may leave permanent skin sequelae. What is New: • Skin sequelae in involuted Infantile hemangiomas are very common. • It is significant to prevent, recognize, and improve skin sequelae of infantile hemangiomas.

Study on the Relationship between Lung Cancer Stromal Cells and Air Cavity Diffusion Based on an Image Acquisition System.

Objective: The study aimed to investigate the role of tumor stromal cells in the pathogenesis of STAS, the relationship between air diffusion (STAS) and tumor stromal cells (TSCs) was studied, and the prognostic significance of TSC and STAS in patients with lung adenocarcinoma was evaluated. Methods: A total of 150 patients with lung cancer diagnosed in the Affiliated Hospital of Jiangsu Province were selected. From the perspective of pathology, medical information technology was used to assist the diagnosis. The data of multiple magnetic resonance images were analyzed by three-dimensional space convolution (CNN), fuzzy neural network (FNN), transfinite learning machine (ELM), and binarization. Result: After data fusion, the specificity and sensitivity of multiple magnetic resonance (MRI) data are significantly higher than those of single MRI data, and the more fusion times, the better the sensitivity and specificity. With the increase in the number of information and data fusion, the proportion of the significant effect and the comprehensive effective rate of patients are on the rise. Multiple MRI data fusion examination and analysis under medical information technology can improve the cure rate of patients, and the 1-year survival rate and the 3-year survival rate of patients have also gradually improved. Conclusion: The MRI data fusion diagnosis method under the application of information technology can improve the sensitivity and specificity of the diagnosis results and comprehensively improve the clinical cure rate and the survival rate at different times of prognosis. In the context of the current big data information age, this multifeature fusion analysis technology is playing a more and more important role in medical treatment. The application of this method and technology not only improves the quality of life of patients but also processes multiple types of data at one time only by using the proposed medical assistant diagnosis model, which can save the diagnosis time to a certain extent. It has effectively realized the medical management and medical service quality and has important promotion significance.

Oncocytoma-Related Gene Signature to Differentiate Chromophobe Renal Cancer and Oncocytoma Using Machine Learning.

Publicly available gene expression datasets were analyzed to develop a chromophobe and oncocytoma related gene signature (COGS) to distinguish chRCC from RO. The datasets GSE11151, GSE19982, GSE2109, GSE8271 and GSE11024 were combined into a discovery dataset. The transcriptomic differences were identified with unsupervised learning in the discovery dataset (97.8% accuracy) with density based UMAP (DBU). The top 30 genes were identified by univariate gene expression analysis and ROC analysis, to create a gene signature called COGS. COGS, combined with DBU, was able to differentiate chRCC from RO in the discovery dataset with an accuracy of 97.8%. The classification accuracy of COGS was validated in an independent meta-dataset consisting of TCGA-KICH and GSE12090, where COGS could differentiate chRCC from RO with 100% accuracy. The differentially expressed genes were involved in carbohydrate metabolism, transcriptomic regulation by TP53, beta-catenin-dependent Wnt signaling, and cytokine (IL-4 and IL-13) signaling highly active in cancer cells. Using multiple datasets and machine learning, we constructed and validated COGS as a tool that can differentiate chRCC from RO and complement histology in routine clinical practice to distinguish these two tumors.

Helical structure motifs made searchable for functional peptide design.

The systematic design of functional peptides has technological and therapeutic applications. However, there is a need for pattern-based search engines that help locate desired functional motifs in primary sequences regardless of their evolutionary conservation. Existing databases such as The Protein Secondary Structure database (PSS) no longer serves the community, while the Dictionary of Protein Secondary Structure (DSSP) annotates the secondary structures when tertiary structures of proteins are provided. Here, we extract 1.7 million helices from the PDB and compile them into a database (Therapeutic Peptide Design database; TP-DB) that allows queries of compounded patterns to facilitate the identification of sequence motifs of helical structures. We show how TP-DB helps us identify a known purification-tag-specific antibody that can be repurposed into a diagnostic kit for Helicobacter pylori. We also show how the database can be used to design a new antimicrobial peptide that shows better Candida albicans clearance and lower hemolysis than its template homologs. Finally, we demonstrate how TP-DB can suggest point mutations in helical peptide blockers to prevent a targeted tumorigenic protein-protein interaction. TP-DB is made available at http://dyn.life.nthu.edu.tw/design/ .

Physalin B reduces Aß secretion through down-regulation of BACE1 expression by activating FoxO1 and inhibiting STAT3 phosphorylation.

Physalin B (PB), one of the major active steroidal constituents of Solanaceae Physalis plants, has a wide variety of biological activities. We found that PB significantly down-regulated ß-amyloid (Aß) secretion in N2a/APPsw cells. However, the underlying mechanisms are not well understood. In the current study, we investigated the changes in key enzymes involved in ß-amyloid precursor protein (APP) metabolism and other APP metabolites by treating N2a/APPsw cells with PB at different concentrations. The results indicated that PB reduced Aß secretion, which was caused by down-regulation of ß-secretase (BACE1) expression, as indicated at both the protein and mRNA levels. Further research revealed that PB regulated BACE1 expression by inducing the activation of forkhead box O1 (FoxO1) and inhibiting the phosphorylation of signal transducer and activator of transcription 3 (STAT3). In addition, the effect of PB on BACE1 expression and Aß secretion was reversed by treatment with FoxO1 siRNA and STAT3 antagonist S3I-201. In conclusion, these data demonstrated that PB can effectively down-regulate the expression of BACE1 to reduce Aßsecretion by activating the expression of FoxO1 and inhibiting the phosphorylation of STAT3.

17ß-Estradiol Exacerbated Experimental Occlusal Interference-Induced Chronic Masseter Hyperalgesia by Increasing the Neuronal Excitability and TRPV1 Function of Trigeminal Ganglion in Ovariectomized Rats.

Pain symptoms in temporomandibular disorders (TMD) predominantly affect reproductive women, suggesting that estrogen regulates pain perception. However, how estrogen contributes to chronic TMD pain remains largely unclear. In the present study, we performed behavioral tests, electrophysiology, Western blot and immunofluorescence to investigate the role and underlying mechanisms of estrogen in dental experimental occlusal interference (EOI)-induced chronic masseter mechanical hyperalgesia in rats. We found that long-term 17ß-estradiol (E2) replacement exacerbated EOI-induced masseter hyperalgesia in a dose-dependent manner in ovariectomized (OVX) rats. Whole-cell patch-clamp recordings demonstrated that E2 (100 nM) treatment enhanced the excitability of isolated trigeminal ganglion (TG) neurons in OVX and OVX EOI rats, and EOI increased the functional expression of transient receptor potential vanilloid-1 (TRPV1). In addition, E2 replacement upregulated the protein expression of TRPV1 in EOI-treated OVX rats. Importantly, intraganglionic administration of the TRPV1 antagonist AMG-9810 strongly attenuated the facilitatory effect of E2 on EOI-induced masseter mechanical sensitivity. These results demonstrate that E2 exacerbated EOI-induced chronic masseter mechanical hyperalgesia by increasing TG neuronal excitability and TRPV1 function. Our study helps to elucidate the E2 actions in chronic myogenic TMD pain and may provide new therapeutic targets for relieving estrogen-sensitive pain.

Serum Levels of Inflammatory Proteins Are Associated With Peripheral Neuropathy in a Cross-Sectional Type-1 Diabetes Cohort.

Chronic low-grade inflammation is involved in the pathogenesis of type-1 diabetes (T1D) and its complications. In this cross-section study design, we investigated association between serum levels of soluble cytokine receptors with presence of peripheral neuropathy in 694 type-1 diabetes patients. Sex, age, blood pressure, smoking, alcohol intake, HbA1c and lipid profile, presence of DPN (peripheral and autonomic), retinopathy and nephropathy was obtained from patient's chart. Measurement of soluble cytokine receptors, markers of systemic and vascular inflammation was done using multiplex immunoassays. Serum levels were elevated in in DPN patients, independent of gender, age and duration of diabetes. Crude odds ratios were significantly associated with presence of DPN for 15/22 proteins. The Odds ratio (OR) remained unchanged for sTNFRI (1.72, p=0.00001), sTNFRII (1.45, p=0.0027), sIL2Rα (1.40, p=0.0023), IGFBP6 (1.51, p=0.0032) and CRP (1.47, p=0.0046) after adjusting for confounding variables, HbA1C, hypertension and dyslipidemia. Further we showed risk of DPN is associated with increase in serum levels of sTNFRI (OR=11.2, p<10), sIL2Rα (8.69, p<10-15), sNTFRII (4.8, p<10-8) and MMP2 (4.5, p<10-5). We combined the serum concentration using ridge regression, into a composite score, which can stratify the DPN patients into low, medium and high-risk groups. Our results here show activation of inflammatory pathway in DPN patients, and could be a potential clinical tool to identify T1D patients for therapeutic intervention of anti-inflammatory therapies.

Tumor-intrinsic and -extrinsic (immune) gene signatures robustly predict overall survival and treatment response in high grade serous ovarian cancer patients.

In the present study, we developed a transcriptomic signature capable of predicting prognosis and response to primary therapy in high grade serous ovarian cancer (HGSOC). Proportional hazard analysis was performed on individual genes in the TCGA RNAseq data set containing 229 HGSOC patients. Ridge regression analysis was performed to select genes and develop multigenic models. Survival analysis identified 120 genes whose expression levels were associated with overall survival (OS) (HR = 1.49-2.46 or HR = 0.48-0.63). Ridge regression modeling selected 38 of the 120 genes for development of the final Ridge regression models. The consensus model based on plurality voting by 68 individual Ridge regression models classified 102 (45%) as low, 23 (10%) as moderate and 104 patients (45%) as high risk. The median OS was 31 months (HR = 7.63, 95% CI = 4.85-12.0, P < 1.0-10) and 77 months (HR = ref) in the high and low risk groups, respectively. The gene signature had two components: intrinsic (proliferation, metastasis, autophagy) and extrinsic (immune evasion). Moderate/high risk patients had more partial and non-responses to primary therapy than low risk patients (odds ratio = 4.54, P < 0.001). We concluded that the overall survival and response to primary therapy in ovarian cancer is best assessed using a combination of gene signatures. A combination of genes which combines both tumor intrinsic and extrinsic functions has the best prediction. Validation studies are warranted in the future.

Computed Tomography-Guided Percutaneous Coblation of the Thoracic Nerve Root for Treatment of Postherpetic Neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is one of the most intractable pain disorders and often does not respond to medication, physical, and interventional procedures. Coblation technology has been demonstrated to have potential for neuralgia, but there are rare reports of the efficacy and security of coblation for PHN. The thoracic segment is the most common predilection part of PHN, so we conducted this long-term study to investigate the results of coblation for the treatment of thoracic PHN. OBJECTIVES: The aim of this study was to determine the efficacy and security of computed tomography (CT)-guided coblation of the thoracic nerve root for treatment of PHN. STUDY DESIGN: Self before-after controlled clinical assessment. SETTING: Department of Pain Management, Xuanwu Hospital, Capital Medical University. METHODS: Seventy-seven patients with thoracic PHN sustained for at least 6 months and refractory to conservative therapy were identified. Patients underwent CT-guided percutaneous coblation to ablate the thoracic nerve root for thoracic PHN. The therapeutic effects were evaluated using a Visual Analog Scale (VAS), medication doses, and pain-related quality of life (QoL) scale before coblation, and at 1 week, and at 1, 3, and 6 months after the procedure. Patients who achieved more than 50% pain relief were defined as responders. In addition, adverse effects were also recorded to investigate the security of this procedure. RESULTS: The VAS score significantly decreased from 7.22 ± 1.15 before the coblation to 3.51 ± 1.12 (P = 0.01), 3.02 ± 1.21 (P = 0.006), 3.11 ± 2.15 (P = 0.014), and 2.98 ± 2.35 (P = 0.008) at 1 week, and at 1, 3, and 6 months after the procedure, respectively. The number of responders were 56 (77.78%), 54 (75%), 55 (76.39%), and 54 (75%) at 1 week, and at 1, 3, and 6 months after the procedure, respectively. The doses of anticonvulsants and analgesics were decreased significantly at all time points after the procedure compared with before treatment (P < 0.05). Patient responses on the Brief Pain Inventory Short Form indicated mean scores that were significantly lower than baseline across all domains of pain interference with QoL at all evaluations (P = 0.001). Most of the patients had mild numbness and it did not affect the daily activities after the procedure. No other severe adverse events occurred during or after the procedure. LIMITATIONS: A single-center study, relatively small number of patients, short duration of review of medical record, and the retrospective study. CONCLUSIONS: CT-guided percutaneous thoracic nerve root coblation is an effective and safe method for the treatment of thoracic PHN, and the procedure can also significantly improve the QoL in patients with PHN.

[Internal and external fixation combined with second stage perforator flap for the treatment of ankle fracture dislocation of Gustilo-Anderson types â ¢B and â ¢ C].

OBJECTIVE: To explore clinical effect of internal and external fixation combined with second-stage perforator fiap for the treatment of ankle fracture dislocation of Gustilo-Anderson types ⅢB and ⅢC. METHODS: From May 2014 to July 2017, 20 patients with Gustilo-Anderson types ⅢB and ⅢC ankle fracture dislocation were treated with internal and external fixation combined with second-stage perforator fiap, including 14 males and 6 females, aged from 18 to 58 years old with an average of (39.0±9.7) years old;17 patients were type ⅢB and 3 patients were type ⅢC according to Gustilo-Anderson classification;4 patients were type A, 7 patients were type B, and 9 patients were type C according to AO classification. The size of wound ranged from 4 cm×3 cm to 20 cm×9 cm. Second-stage perforator flap, 11 patients were performed with posterior tibial artery perforator flap, 5 patients were performed with fibular artery perforator flap, 1 patient was performed with anterior ankle flap, and 3 patients were performed with posterior tibial artery perforator flap combined with fibular artery perforator flap. Postoperative wound healing, flap survival and fracture healing were observed, AOFAS score was used to evaluate at the latest follow up. RESULTS: All limbs were preserved successfully without amputation. Nine patients occurred superficial infection without deep infection and osteomyelitis occurring. The flaps of 19 patients survived. All patients were followed up for 6 to 18 months with an average of (12.0±2.9) months. The flaps healed well without sinus tract, bone exposure and bone disunion occurring. Fracture healing time ranged from 4 to 10 months with an average of (6.6±1.7) months. PostoperativeAOFAS score was 76.7± 16.4, among which 4 patients got excellent result, 11 patients good, 3 patients fair, and 2 poor. CONCLUSION: Internal and external fixation combined with second stage perforator fiap for the treatment of ankle fracture dislocation of Gustilo-Anderson types ⅢB and ⅢC could effectively close the wound, improve fracture healing and restore appearance and function of limbs to the maximum.

Identification of a transcriptomic signature with excellent survival prediction for squamous cell carcinoma of the cervix.

Survival for patients with newly diagnosed cervical cancer has not significantly improved over the past several decades. We sought to identify a clinically relevant set of prognostic genes for squamous cell carcinoma of the cervix (SCCC), the most common cervical cancer subtype. Using RNA-sequencing data and survival data from 203 patients in The Cancer Genome Atlas (TCGA), we conducted a series of analyses using different decile cutoffs for gene expression to identify genes that could indicate large and consistent survival differences across different decile cutoffs of gene expression. Those analyses identified 42 high-risk genes. A patient's survivability could be estimated by simply counting the number of high-risk genes with extremely high expression (above the 90th percentile) or estimating a transcriptomic risk score (TRS) using a machine learning algorithm with 9 of the 42 genes. On multivariate analysis, the significant predictors of mortality included high TRS (HR = 44.8), stage IV (HR = 28.1), intermediate TRS (HR = 4.75), and positive lymph node status (HR = 2.92). Approximately 18% of earlier-stage patients were identified as a poor-prognosis subgroup with high TRS. In patients with SCCC, transcriptomic risk appears to better predict survival than clinical prognostic factors, including stage.

Antifogging/Antibacterial Coatings Constructed by N-Hydroxyethylacrylamide and Quaternary Ammonium-Containing Copolymers.

Endoscopic surgery has gained widespread applications in various clinical departments, and endoscope surfaces with antifogging and antibacterial properties are essential for elaborate procedures. In this work, novel antifogging/antibacterial coatings were developed from a cationic copolymer and a hydrophilic copolymer, polyhedral oligomeric silsesquioxane-poly(quaternary ammonium compound-co-2-aminoethyl methacrylate hydrochloride) [POSS-P(QAC-co-AEMA)] and poly(N-hydroxyethylacrylamide-co-glycidyl methacrylate) [P(HEAA-co-GMA)] via a facile and green blending method. Such transparent coatings showed excellent antifogging performance under both in vitro and in vivo fogging conditions, mainly attributed to the high water-absorbing capability of HEAA and QAC. Antibacterial assays proved that the blending coatings had a superior antibacterial property, which could be improved with the proportion of POSS-P(QAC-co-AEMA) because of the bactericidal efficiency of cationic QAC. Meanwhile, owing to the high hydratability of HEAA, the blending coatings exhibited a bacteria-repelling property. By simply tuning the blending ratio of POSS-P(QAC-co-AEMA) and P(HEAA-co-GMA), the comprehensive bacteria-killing and bacteria-repelling properties of the coatings were achieved. Moreover, after incubating with red blood cells, the prepared blending coatings presented a lower hemolytic rate of less than 5%. The findings provided a potential means for addressing the challenge of fogging and bacterial contamination occurring in endoscopic lenses and other medical devices.

Coenzyme Binding Site Analysis of an Isopropanol Dehydrogenase with Wide Substrate Spectrum and Excellent Organic Solvent Tolerance.

NAD(P)H-dependent enzymes are ideal biocatalysts for the industrial production of chiral compounds, such as chiral alcohols, chiral amino acids, and chiral amines; however, efficient strategies for the regeneration of coenzyme are expected as costly of the coenzymes. Herein, a solvent-tolerant isopropanol dehydrogenase (IDH) showing lower similarity (37%) with other proteins was obtained and characterized. The enzyme exhibits high catalysis ability of its substrates methanol, ethanol, ethylene glycol, glycerol, isopropanol, n-butanol, isobutanol, and acetone. And it has good adaptability in organic solvents (isopropanol, acetonitrile, acetone, and acetophenone). Interaction force and the corresponding amino acid residues between IDH and NAD+ or NADP+ were parsed by docking. The wide substrate spectrum, excellent organic solvent tolerance, and good biocatalytic activity make the excavated enzyme a promising biocatalyst for the production of chiral compounds industrially and the construction of coenzyme regeneration systems in aqueous organic phase or organic phase.

A Novel Method to Enhance Dynamic Rhinoplasty Outcomes: Double "V" Carving for Alloplastic Grafts.

Augmentation rhinoplasty is one of the most common plastic surgery procedures performed in Asia. Most Asian patients desire not only a natural-looking nose but also a nose with natural feel. Achieving such rhinoplasty outcomes with grafts has been a challenge for surgeons due to rigidity of grafting material. We propose a novel technique to address this limitation. A total of 200 healthy adult patients aged from 18 to 25 years were randomly chosen and classified into 5 groups: A, B, C, D, and control. Each group included 40 patients. The patients assigned to conventional grafting underwent rhinoplasty with L-shaped silicone prosthesis (group A) or expanded polytetrafluoroethylene (e-PTFE; group B), using traditional carving methods. The patients assigned to dynamic rhinoplasty underwent silicone (group C) or e-PTFE grafts (group D) using the modified double "V" method, which involves removing bilateral wedges from the graft to decrease rigidity. Patients in control group do not undergo the surgery. A 3-dimensional raster surface scanner was used to capture the images of the patients accurately and nasal mobility was measured. Subjective evaluations were carried out by a series of questionnaires asked to the patients. The angle α of nasal mobility was significantly lower in conventional grafting (23.09 [5.34] mm for silicone and 17.88 [4.96] mm for e-PTFE) versus the "V" carving (30.53 [3.76] mm for silicone and 23.77 [4.53] mm for e-PTFE; P < .05). The double "V" carving method is a simple, effective, and practical method for improving dynamic nasal outcomes in patient undergoing augmentation rhinoplasty.

Clinical effect and safety of dendritic cell-cytokine-induced killer cell immunotherapy for pancreatic cancer: a systematic review and meta-analysis.

BACKGROUND: Although promising results have recently been reported using dendritic cells (DCs) and cytokine-induced killer cells (CIKs) to treat pancreatic cancer (PC), its clinical effect and safety are associated with some controversy, and lack sufficient evidence. Here, we conducted a meta-analysis of 21 clinical trials to better evaluate the efficacy of DC-CIK immunotherapy in clinical practice to treat PC. METHODS: PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang Data Knowledge Service Platform (WANFANG Data) were searched to identify clinical trials that used DC-CIK immunotherapy for PC. Meta-analysis was performed using RevMan 5.3 and Stata 12.0. RESULTS: A total of 21 clinical trials involving 1549 patients were included. Compared with traditional treatment, DC-CIK immunotherapy improved and increased the clinical indices such as complete remission, partial remission, overall response rate, disease control rate, overall survival (0.5-y OS, 1-y OS, 1.5-y OS, 2-y OS and 3-y OS), interferon γ and CD3+, CD4+, CD4+/CD8+ and CD3+CD56+ lymphocyte. Additionally, DC-CIK immunotherapy reduced stable disease, progression disease, mortality, CD8+, CD4+CD25+CD127 low lymphocyte and interleukin-4. Furthermore, it showed a low incidence of adverse reactions (22%). CONCLUSION: In contrast to traditional therapy, DC-CIK immunotherapy not only shows improved short-term effect, long-term effect and immunologic function, but also reduces mortality and negative immunoregulatory index, and shows mild adverse reactions. This is the first study to evaluate the clinical effect and safety of DC-CIK immunotherapy for PC, and it indicated that DC-CIK immunotherapy may be suitable for patients with advanced PC or intolerance to radiotherapy and chemotherapy.

A pan-cancer perspective of matrix metalloproteases (MMP) gene expression profile and their diagnostic/prognostic potential.

IMPLICATION: By understanding Matrix Metalloprotease (MMP) dysregulation from a pan-cancer perspective, this study sheds light on the diagnostic potentials of MMPs across multiple neoplasms. BACKGROUND: MMPs are intriguing genes related to cancer disease progression, functional promotion of angiogenesis, invasion, metastasis, and avoidance of immune surveillance. Many studies have noted these genes are frequently upregulated in cancer. However, expression patterns of all MMPs and their diagnostic and prognostic potential have not been investigated in a pan-cancer perspective. METHODS: The Cancer Genome Atlas (TCGA) data were used to evaluate diagnostic and prognostic potential of 24 MMPs in fifteen different cancer types. Gene expression measured by RNA-seq was analyzed by differential expression, hierarchical clustering, and ROC analysis for individual genes and in combination. RESULTS: MMP1, MMP9, MMP10, MMP11, and MMP13 were almost universally upregulated across all cancers, with significant (p < 0.05) fold change (FC > 2) in ten of fifteen cancers. MMP3, MMP7, MMP12 and MMP14) are significantly up-regulated in at least 10 cancer types. Interestingly, MMP2, MMP7, MMP23B, MMP27 and MMP28) are significantly down-regulated in seven to nine cancer types. Multiple MMPs possess AUC's > 0.9 in more than one cancer. However, survival analyses suggest that the prognostic value of MMPs is limited to clear cell renal carcinoma. CONCLUSIONS: Most MMPs have consistently increased gene expression across cancers, while several MMPs have consistently decreased expression in several cancer types. Many MMPs have diagnostic value individually or in combination, while the prognostic value of MMPs is restricted to one subtype of kidney cancer.

Nerve coblation for treatment of trigeminal neuralgia: A case report.

BACKGROUND: Trigeminal neuralgia (TN) is a severe type of neuropathic pain which is often inadequately managed using conventional therapies. In this report, we present the first case of TN treated with gasserian ganglion nerve coblation (NC). CASE SUMMARY: A 58-year-old man presented with right facial pain, mostly localized in the right zygomatic zone, alveolar region, and jaws. Similar to acupuncture and shock pain, the pain lasted about five seconds after each attack before resolving unaided. A diagnosis of TN was made, after which treatment with acupuncture therapy and oral carbamazepine was given. However, the pain was not satisfactorily controlled. Subsequently, gasserian ganglion NC of the right trigeminal nerve guided by computed tomography (CT) was performed on the patient. Following this procedure, the right zygomatic, alveolar, submandibular, and cheek pain disappeared completely. The right zygomatic and alveolar areas experienced mild numbness (level II). At 1-, 2-, 3-, and 6-mo follow-ups after surgery, the patient was painless and the numbness score was level I. CONCLUSION: CT-guided gasserian ganglion (NC) is an effective treatment for TN and is associated with less or no postoperative numbness or hypoesthesia in comparison with current standard-of-care approaches.

Comparative STAT3-Regulated Gene Expression Profile in Renal Cell Carcinoma Subtypes.

Renal cell carcinomas (RCC) are heterogeneous and can be further classified into three major subtypes including clear cell, papillary and chromophobe. Signal transducer and activator of transcription 3 (STAT3) is commonly hyperactive in many cancers and is associated with cancer cell proliferation, invasion, migration, and angiogenesis. In renal cell carcinoma, increased STAT3 activation is associated with increased metastasis and worse survival outcomes, but clinical trials targeting the STAT3 signaling pathway have shown varying levels of success in different RCC subtypes. Using RNA-seq data from The Cancer Genome Atlas (TCGA), we compared expression of 32 STAT3 regulated genes in 3 RCC subtypes. Our results indicate that STAT3 activation plays the most significant role in clear cell RCC relative to the other subtypes, as half of the evaluated genes were upregulated in this subtype. MMP9, BIRC5, and BCL2 were upregulated and FOS was downregulated in all three subtypes. Several genes including VEGFA, VIM, MYC, ITGB4, ICAM1, MMP1, CCND1, STMN1, TWIST1, and PIM2 had variable expression in RCC subtypes and are potential therapeutic targets for personalized medicine.