Proteomics analyses of acute kidney injury biomarkers in a rat exertional heat stroke model.

The frequency of exertional heat stroke (EHS) increases with the gradual elevation of global temperatures during summer. Acute kidney injury (AKI) is a common complication of EHS, and its occurrence often indicates the worsening of a patient's condition or a poor prognosis. In this study, a rat model of AKI caused by EHS was established, and the reliability of the model was evaluated by HE staining and biochemical assays. The expression of kidney tissue proteins in the EHS rats was analyzed using label-free liquid chromatography-tandem mass spectrometry. A total of 3,129 differentially expressed proteins (DEPs) were obtained, and 10 key proteins were finally identified, which included three upregulated proteins (Ahsg, Bpgm, and Litaf) and seven downregulated proteins (medium-chain acyl-CoA synthetase 2 (Acsm2), Hadha, Keg1, Sh3glb1, Eif3d, Ambp, and Ddah2). The qPCR technique was used to validate these 10 potential biomarkers in rat kidney and urine. In addition, Acsm2 and Ahsg were double-validated by Western blotting. Overall, this study identified 10 reliable biomarkers that may provide potential targets for the treatment of AKI caused by EHS.

An integrated network pharmacology approach reveals that Darutigenol reduces inflammation and cartilage degradation in a mouse collagen-induced arthritis model by inhibiting the JAK-STAT3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Darutigenol (DL) is a natural active product derived from the Chinese herbal medicine Sigesbeckia glabrescens (Makino) Makino. It is administered as a traditional Chinese medicine (TCM) to dispel rheumatism, benefit the joints, and detoxify. However, its potential mechanism in the treatment of rheumatoid arthritis (RA) remains unknown. AIMS OF THE STUDY: The objectives of this research were to determine the effects and elucidate the modes of action of DL on RA-related joint inflammation. MATERIALS AND METHODS: Network pharmacology and molecular docking were used to screen and validate candidate DL targets for RA treatment, respectively. A DBA/1 mouse rheumatoid arthritis model was induced with bovine type II collagen. Intragastric DL administration was followed by the calculation of the clinical arthritis index. A section of the ankle joint was excised and stained and the pathological changes in it were observed. Enzyme-linked immunosorbent assays (ELISA) and western blotting (WB) were used to clarify the mechanisms of DL in RA treatment. RESULTS: DL effectively attenuated the inflammation, mitigated the articular cartilage degradation, and bone erosion, and alleviated the inflammatory joints associated with RA. Network pharmacology screened six key targets of DL while molecular docking revealed that it docked well with its protein targets. The DL treatment group presented with significantly less ankle joint redness and swelling, a lower arthritis index scores and serum and bone marrow supernatant IL-6 levels, more complete ankle joint surfaces, and less synovial inflammation, cartilage degradation, and bone erosion than the collagen-induced arthritis (CIA) group. The DL treatment also substantially downregulated the Janus kinase (JAK)1, JAK3, matrix metalloproteinase (MMP)2, MMP9, and phospho-signal transducer and activator of transcription (p-STAT)3 proteins in the joints. CONCLUSIONS: To the best of our knowledge, the present work was the first to demonstrate that DL has significant anti-inflammatory efficacy and reduces cartilage degradation and bone erosion. It also demonstrated that the anti-RA effect of DL may be explained by its ability to inhibit joint inflammation and reduce articular cartilage degradation through the interleukin (IL)-6/JAK1,3/STAT3 axis and downregulate MMP2 and MMP9. Hence, DL might play a therapeutic role in a mouse RA model.

A Comparative Review of the Outcome Following MVD and PBC in Patients with Trigeminal Neuralgia.

BACKGROUND: This study aims to systematically review the treatment outcomes of percutaneous balloon compression (PBC) and microvascular decompression (MVD) in patients with trigeminal neuralgia. METHODS: A systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was performed using PubMed, Embase, and Cochrane Central Registry of Controlled Trials databases. Only those articles with more than 5 years' follow-up length were included in this investigation. To uniformly assess the postoperative outcome, we defined pain relief as totally pain free, while the postoperative hospitalization and last follow-up period were defined as early and long term, respectively. The facial numbness was quantified with Barrow Neurological Institute Pain Intensity Score (BNI). RESULTS: After database searching and screening, 7,797 cases were finally included according to the criteria. The early pain relief rates were 94.1% (1,551/1,649) and 89.9% (4,962/5,482) following PBC and MVD (odds ratio [OR] = 0.603; p < 0.05), while the long-term rates were 58.1% (921/1,566) and 74.9% (4,549/6,074; OR = 2.089; p < 0.05), respectively. Although a significant higher facial numbness occurred in the PBC group in the early stage, it was mostly diminished 5 years later compared with the MVD group. At long-term follow-up, hypoacusis and facial palsy occurred more often in the MVD group (p < 0.05). CONCLUSIONS: Both MVD and PBC provide a satisfactory outcome for the patients in the long term. As a simple, safe, and reliable technique, PBC should be considered as a viable alternative.

Progress in diagnosis and treatment of ovarian metastases in rectal cancer / 中华胃肠外科杂志

Rectal cancer is the most common tumor of digestive tract. For female patients, ovarian metastasis ranks the second place in intraperitoneal organ metastasis. Its symptoms are occult, easily missed and insensitive to systemic treatment, so the prognosis is poor. Surgery is the treatment of choice for patients with rectal ovarian metastases, whether R0 resection is possible or not, and reducing tumor load is associated with better prognosis. With the continuous development of hyperthermic intraperitoneal chemotherapy (HIPEC), tumor reduction can reach the cellular level, which can significantly improve survival. Prophylactic ovariectomy remains a controversial issue in patients at high risk of ovarian metastasis. In this review, we summarize the diagnosis, treatment and prevention strategies of rectal cancer ovarian metastases, hoping to provide some reference for clinical practice.

Association of chronic obstructive pulmonary disease with mild cognitive impairment and dementia risk: A systematic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common public health issue that has been linked to cognitive dysfunction. AIM: To investigate the relationship between COPD and a risk of mild cognitive impairment (MCI) and dementia. METHODS: A comprehensive literature search of the PubMed, Embase, Google Scholar, and Cochrane Library electronic databases was conducted. Pooled odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CIs) were calculated using a random or fixed effects model. Studies that met the inclusion criteria were assessed for quality using the Newcastle Ottawa Scale. RESULTS: Twenty-seven studies met all the inclusion criteria. Meta-analysis yielded a strong association between COPD and increased risk of MCI incidence (OR = 2.11, 95%CI: 1.32-3.38). It also revealed a borderline trend for an increased dementia risk in COPD patients (OR = 1.16, 95%CI: 0.98-1.37). Pooled hazard ratios (HR) using adjusted confounders also showed a higher incidence of MCI (HR = 1.22, 95%CI: -1.18 to -1.27) and dementia (HR = 1.32, 95%CI: -1.22 to -1.43) in COPD patients. A significant lower mini-mental state examination score in COPD patients was noted (MD = -1.68, 95%CI: -2.66 to -0.71). CONCLUSION: Our findings revealed an elevated risk for the occurrence of MCI and dementia in COPD patients. Proper clinical management and attention are required to prevent and control MCI and dementia incidence in COPD patients.

PPARß down-regulation is involved in high glucose-induced endothelial injury via acceleration of nitrative stress.

Endothelial injury plays a vital role in vascular lesions from diabetes mellitus (DM). Therapeutic targets against endothelial damage may provide critical venues for the treatment of diabetic vascular diseases. Peroxisome proliferator-activated receptor ß (PPARß) is a crucial regulator in DM and its complications. However, the molecular signal mediating the roles of PPARß in DM-induced endothelial dysfunction is not fully understood. The impaired endothelium-dependent relaxation and destruction of the endothelium structures appeared in high glucose incubated rat aortic rings. A high glucose level significantly decreased the expression of PPARß and endothelial nitric oxide synthase (eNOS) at the mRNA and protein levels, and reduced the concentration of nitric oxide (NO), which occurred in parallel with an increase in the expression of inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine. The effect of high glucose was inhibited by GW0742, a PPARß agonist. Both GSK0660 (PPARß antagonist) and NG-nitro-l-arginine-methyl ester (NOS inhibitor) could reverse the protective effects of GW0742. These results suggest that the activation of nitrative stress may, at least in part, mediate the down-regulation of PPARß in high glucose-impaired endothelial function in rat aorta. PPARß-nitrative stress may hold potential in treating vascular complications from DM.

Euphorfinoids E-L: Diterpenoids from the roots of Euphorbia fischeriana with acetylcholinesterase inhibitory activity.

Eight undescribed diterpenoids, euphorfinoids E-L, together with twelve known analogues, were isolated from the roots of wild Euphorbia fischeriana. Their structures and absolute configurations were elucidated by a combination of NMR, MS, ECD, and X-ray diffraction analyses. The plausible biosynthetic pathway of 1 was also proposed. The isolated compounds displayed moderate inhibitory activity against acetylcholinesterase (AChE) with 50% inhibiting concentration (IC50) values of 6.23-192.38 µM.

Anticholinergics combined with alpha-blockers for treating lower urinary tract symptoms related to benign prostatic obstruction.

BACKGROUND: Lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) represent one of the most common clinical complaints in men. Alpha-blockers are widely used as first-line therapy for men with LUTS secondary to BPO, but up to one third of men report no improvement in their LUTS after taking alpha-blockers. Anticholinergics used in addition to alpha-blockers may help improve symptoms but it is uncertain how effective they are.  OBJECTIVES: To assess the effects of combination therapy with anticholinergics and alpha-blockers in men with LUTS related to BPO. SEARCH METHODS: We performed a comprehensive search of medical literature, including the Cochrane Library, MEDLINE, Embase, and trials registries, with no restrictions on the language of publication or publication status. The date of the latest search was 7 August 2020. SELECTION CRITERIA: We included randomized controlled trials. Inclusion criteria were men with LUTS secondary to BPO, ages 40 years or older, and a total International Prostate Symptom Score of 8 or greater. We excluded trials of men with a known neurogenic bladder due to spinal cord injury, multiple sclerosis, or central nervous system disease, and those examining medical therapy for men who were treated with surgery for BPO. We performed three comparisons: combination therapy versus placebo, combination therapy versus alpha-blockers monotherapy, and combination therapy versus anticholinergics monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, extracted data, and assessed risk of bias. We performed statistical analyses using a random-effects model and interpreted data according to the Cochrane Handbook for Systematic Reviews of Interventions. We used the GRADE approach to rate the certainty of evidence. MAIN RESULTS: We included 23 studies with 6285 randomized men across three comparisons. The mean age of participants ranged from 54.4 years to 73.9 years (overall mean age 65.7 years). Of the included studies, 12 were conducted with a single-center setting, while 11 used a multi-center setting. We only found short-term effect (12 weeks to 12 months) of combination therapy based on available evidence. Combination therapy versus placebo: based on five studies with 2369 randomized participants, combination therapy may result in little or no difference in urologic symptom scores (mean difference (MD) -2.73, 95% confidence interval (CI) -5.55 to 0.08; low-certainty evidence). We are very uncertain about the effect of combination therapy on quality of life (QoL) (MD -0.97, 95% CI -2.11 to 0.16; very low-certainty evidence). Combination therapy likely increases adverse events (risk ratio (RR) 1.24, 95% CI 1.04 to 1.47; moderate-certainty evidence); based on 252 adverse events per 1000 participants in the placebo group, this corresponds to 61 more adverse events (95% CI 10 more  to 119 more) per 1000 participants treated with combination therapy. Combination therapy versus alpha-blockers alone: based on 22 studies with 4904 randomized participants, we are very uncertain about the effect of combination therapy on urologic symptom scores (MD -2.04, 95% CI -3.56 to -0.52; very low-certainty evidence) and QoL (MD -0.71, 95% CI -1.03 to -0.38; very low-certainty evidence). Combination therapy may result in little or no difference in adverse events rate (RR 1.10, 95% CI 0.90 to 1.34; low-certainty evidence); based on 228 adverse events per 1000 participants in the alpha-blocker group, this corresponds to 23 more adverse events (95% CI 23 fewer to 78 more) per 1000 participants treated with combination therapy. Combination therapy compared to anticholinergics alone: based on three studies with 1218 randomized participants, we are very uncertain about the effect of combination therapy on urologic symptom scores (MD -3.71, 95% CI -9.41 to 1.98; very low-certainty evidence). Combination therapy may result in an improvement in QoL (MD -1.49, 95% CI -1.88 to -1.11; low-certainty evidence). Combination therapy likely results in little to no difference in adverse events (RR 1.26, 95% CI 0.81 to 1.95; moderate-certainty evidence); based on 115 adverse events per 1000 participants in the anticholinergic alone group, this corresponds to 4 fewer adverse events (95% CI 7 fewer to 13 more) per 1000 participants treated with combination therapy. AUTHORS' CONCLUSIONS: Based on the findings of the review, combination therapy with anticholinergics and alpha-blockers are associated with little or uncertain effects on urologic symptom scores compared to placebo, alpha-blockers, or anticholinergics monotherapy. However, combination therapy may result in an improvement in quality of life compared to anticholinergics monotherapy, but an uncertain effect compared to placebo, or alpha-blockers. Combination therapy likely increases adverse events compared to placebo, but not compared to alpha-blockers or anticholinergics monotherapy. The findings of this review were limited by study limitations, inconsistency, and imprecision. We were unable to conduct any of the predefined subgroup analyses.

Heterogeneity in PD-L1 expression in malignant peritoneal mesothelioma with systemic or intraperitoneal chemotherapy.

Programmed death-ligand 1 (PD-L1) expression has been described in patients with malignant peritoneal mesothelioma (MPM), but treatment strategies utilising immune checkpoint inhibition are yet to be defined. Here, we examine levels of PD-L1 expression in MPM patients treated with systemic and/or intraperitoneal chemotherapy using tissue from patient tumour biopsies or resections at multiple time points. We found the mean PD-L1 expression was higher in those with a germline mutation and/or those with a higher somatic mutation burden. Moreover, PD-L1 expression was lower in patients who had received prior chemotherapy as compared to the treatment-naive cohort. Twenty patients who received chemotherapy, either systemic and/or peritoneal, between PD-L1 measurements showed marked heterogeneity. Six (30%) patients demonstrated upregulation of PD-L1, while eight (40%) demonstrated downregulation. Heterogeneity in PD-L1 expression in MPM before and after cytotoxic therapies may present an additional consideration when initiating immune checkpoint inhibition in this rare and challenging disease.

Overview on Traditional Chinese Medicine syndrome differentiation and treatment of Coronavirus Disease 2019 (COVID-19) / 国际中医中药杂志

This paper reviews the Traditional Chinese Medicine (TCM) diagnosis and treatments for Coronavirus Disease 2019 (COVID-19) and the theories of different experts in TCM. The pathogenesis of COVID-19 involves dampness, toxin, heat, cold, blood stasis and deficiency. Dampness and poison were the core pathological factors. The treatment is based on the situation of patients in different regions and different stages of the disease, and focuses on dampness and toxin, with the purpose of eliminating evil and consolidating the foundation. Oral TCM prescriptions such as Qingfei-Paidu Decoction, Qingfei-Touxie-Fuzheng Decoction, Lianhua-Qingwen capsule (granule) show good curative effect. TCM non drug therapies, such as acupuncture, moxibustion, acupoint application, ear acupuncture, traditional exercises, etc., are mostly aimed at light, ordinary and convalescent patients, which can improve symptoms. However, high-quality TCM research is still needed.

Detection of oropharyngeal sensory function in normal population / 中华耳鼻咽喉头颈外科杂志

Objective: To study the oropharyngeal sensory function by Current Perception Threshold(CPT) detection, to explore the detection method of oropharyngeal sensory function in normal population, and to analyze the possible influencing factors. Methods: Fifty-eight normal subjects were included prospectively in this study. Age, gender, body mass index (BMI) were collected. The age of the subjects ranged from 20 to 76 (43.27±13.52) years old. There were 34 females with 17 in childbearing period and 17 in menopause; and 24 males were included.In all the cases, 6 cases were in low BMI, 39 cases were in normal BMI, 10 cases were overweight and 3 cases were suffering from obesity. The CPT system of Neurometer was used to stimulate bilateral palatoglossal arch and tongue base.The current used was 2000 Hz, 250 Hz and 5 Hz respectively.The function of type Aβ, Aδ and C sensory nerve fibers were tested and the CPT values were recorded.The values were inversely proportional to pharyngeal sensation function.To evaluate the oropharyngeal sensory function of the subjects, the CPT values of each frequency at each testing point were compared. SPSS 25.0 software was used for statistical analysis. Results: The CPT value of palatoglossal arch was significantly lower than that of tongue base (t=-2.58,-2.65,-2.54,-2.47,-2.37,-2.77,P<0.05), 2 000 Hz>250 Hz>5 Hz, and there was no significant difference between left and right sides(t=-0.03,-0.51,-0.49,0.06,-0.16,0.13,P>0.05). The CPT value of male was slightly higher than that of female (t=0.92,1.55,0.27,0.78,1.44,1.26,0.35,0.77,1.27,0.24,0.78,0.96,P>0.05). The CPT values of women in childbearing period were significantly less than those in menopausal women (t=-3.90,-3.64,-2.14,-4.20,-4.28,-4.28,-3.52,-4.46,-3.41,-3.63,-4.66,-2.86,P<0.05). The CPT value increased with age, and the values of all frequency of 20 to 30 years old group was significantly lower than those of subjects over 40 years old at each point (The t values of bilateral palatoglossal arch at 2 000 Hz were -5.57,-6.22,-10.18,-11.00;the t values of bilateral palatoglossal arch at 250 Hz were -6.39,-8.79,-6.39,-15.61;the t values of bilateral palatoglossal arch at 5 Hz were -7.09, -5.57, -9.26, -15.23;the t values of tongue base at 2 000 Hz were -3.11,-3.88,-7.60,-8.55;the t values of tongue base at 250 Hz were -6.31,-10.59,-8.52,-10.60;the t values of tongue baseat 5 Hz were -6.69,-5.09,-8.70,-7.07,P<0.05).The values at all frequencies and testing points of 30-40 years old group were significantly lower than those of all subjects over 60 years old (The t values of bilateral palatoglossal arch at 2 000 Hz were -10.91,-12.42;the t values of bilateral palatoglossal arch at 250 Hz were -6.25,-10.87;the t values of bilateral palatoglossal arch at 5 Hz were -5.53,-11.01;the t values of tongue base at 2 000 Hz were -8.62,-10.12;the t values of tongue base at 250 Hz were -6.89,-7.82;the t values of tongue base at 5 Hz were -6.13,-6.48,P<0.05). Conclusions: CPT can be used to evaluate oropharyngeal sensory function. The sensitivity of tongue base is lower than that of palatoglossal arch, there is no significant difference in oropharyngeal sensory function between male and female,between left and right sides. There are many factors influencing oropharyngeal sensory function. Age, hormone level changes may affect the sensitivity of oropharyngeal sensory function.

Strategies and reflections on platelet-based targeted therapy for tumor / 药学学报

In the past few decades, our understanding of platelets has made great progress. Platelets play an unexpected central role in cancer and greatly affect the behavior of cancer cells. At the same time, the physiology and phenotype of platelets are also affected by cancer cells. Therefore, platelet-based tumor targeted therapy strategies have attracted the attention of researchers, but the limitations of their application require more attention. In this paper, the strategies of platelet-based tumor targeted therapy are summarized, and the strategies of platelet mimicking nanocarrier delivery, platelet hitch riding, platelet membrane coating biomimetic and engineered platelet targeting are mainly introduced. The easy activation, hard storage and unknown functional and phenotypic changes of platelets were discussed. At the same time, the strategy of platelet-based targeted tumor therapy is reviewed from theoretical basis and practical application. The development potential of platelets in the field of tumor diagnosis and treatment is discussed, which will provide some theoretical reference for the study of platelet-related tumor diagnosis and targeted therapy.

4-Hydroxyacetophenone modulates the actomyosin cytoskeleton to reduce metastasis.

Metastases are the cause of the vast majority of cancer deaths. In the metastatic process, cells migrate to the vasculature, intravasate, extravasate, and establish metastatic colonies. This pattern of spread requires the cancer cells to change shape and to navigate tissue barriers. Approaches that block this mechanical program represent new therapeutic avenues. We show that 4-hydroxyacetophenone (4-HAP) inhibits colon cancer cell adhesion, invasion, and migration in vitro and reduces the metastatic burden in an in vivo model of colon cancer metastasis to the liver. Treatment with 4-HAP activates nonmuscle myosin-2C (NM2C) (MYH14) to alter actin organization, inhibiting the mechanical program of metastasis. We identify NM2C as a specific therapeutic target. Pharmacological control of myosin isoforms is a promising approach to address metastatic disease, one that may be readily combined with other therapeutic strategies.

[Expression Level of FLRG in Colon Cancer Tissue and Its Clinical Significance].

OBJECTIVE: To investigate the expression of follistatin related gene ( FLRG) in colon cancer and its relationship with clinicopathological features of colon cancer. METHODS: The cancer tissue, paracancerous tissue and normal tissue were collected from 80 patients with colon cancer who underwent radical operation from December 2018 to December 2019. Immunohistochemistry and Real-time PCR were carried out to examine the expression of FLRG and the clinical implications of FLRG was further analyzed. RESULTS: The expression of FLRG in colon cancer tissues was significantly higher than that in paracancerous tissues and normal tissues ( P<0.05), and the expression of FLRG in paracancerous tissues was significantly higher than that in normal tissues ( P<0.05). There was no significant difference in the expression of FLRG among colon cancer patients with different sex, age, tumor growth location and differentiation degree ( P>0.05). The expression level of FLRG in patients with distant metastasis was higher than that in patients without distant metastasis ( P<0.05), and the expression level of FLRG in patients with late clinical stage (stage Ⅲ and Ⅳ) was higher than that in patients with earlier clinical stage (stage Ⅰ and Ⅱ) ( P<0.05). CONCLUSION: FLRG is up-regulated in colon cancer tissue, which may be involved in the regulation of tumor development. FLRG may be a potential prognostic target.

Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling.

Most studies focus on how intestinal microbiota influence cancer immunotherapy through activating gut immunity. However, immunotherapies related to innate responses such as CD47 blockade rely on the rapid immune responses within the tumor microenvironment. Using one defined anaerobic gut microbiota to track whether microbiota interact with host immunity, we observed that Bifidobacterium facilitates local anti-CD47 immunotherapy on tumor tissues through the capacity to accumulate within the tumor microenvironment. Systemic administration of Bifidobacterium leads to its accumulation within the tumor and converts the nonresponder mice into responders to anti-CD47 immunotherapy in a stimulator of interferon genes (STING)- and interferon-dependent fashion. Local delivery of Bifidobacterium potently stimulates STING signaling and increases cross-priming of dendritic cells after anti-CD47 treatment. Our study identifies the mechanism by which gut microbiota preferentially colonize in tumor sites and facilitate immunotherapy via STING signaling.

Peritoneal Metastases in Colorectal Cancer: Biology and Barriers.

BACKGROUND: Advances in the molecular biology of tumor metastasis have paralleled the evolution in the management of metastatic disease from colorectal cancer. In this review, we summarize the current understanding of the mechanism of colorectal cancer metastases, in particular that of peritoneal metastases, as well as clinical data on the treatment of this disease. METHODS: A review of relevant English literature using MEDLINE/PubMed on the biology of colorectal cancer metastases, determinants of oligometastasis, and use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of metastatic colorectal cancer is presented. RESULTS: Recognition of oligometastasis in the evolution of colorectal peritoneal metastases provides the theoretical framework for which cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy is considered. Clearly, a subset of patients benefit from peritoneal metastasectomy. CONCLUSION: Advances in cancer biology and clinical imaging promise to expand the role of cytoreductive surgery with or without intraperitoneal chemotherapy in the management of peritoneal metastases from colorectal cancer.

Clinical Application of Temporary External Fixator for Immediate Mandibular Reconstruction.

Immediate mandibular reconstruction is always necessary for the patients receiving segmental mandibulectomy to recover the facial contour and function of occlusion. When 3D modeling is unavailable, temporary external fixator is necessary to maintain the occlusion relationship and facial contour. In this study, we introduce the clinical application of temporary external fixator for immediate mandibular reconstruction in patients receiving segmental mandibulectomy, which consists of 2 anchor claws, 2 all-round retentive arms, and 1 central locking structure. From August 2016 to September 2017, temporary external fixator was applied in 13 patients. Clinical data of gender, age, surgical procedure, duration of operation, and clinical outcomes were recorded and analyzed. Among the 13 patients, there were 4 men and nine women whose ages ranged from 21 to 64 (mean 47.7) years old. There were 9 benign and 4 malignant lesions. All lesions expended at the buccal side of mandible. 12 fibular flaps and 1 vascularized iliac bone graft were used. The mandibular defect ranged from 6 to 14 (mean 10) cm. The operation duration of surgery ranged from 5 to 10 (mean 7) hours. All flaps survived with primary healing. The occlusion and facial contour were good, without significant changes of the length of mandibular body and width of mandible before and after surgery. No functional sequelae were noted at the donor sites. From these results, the temporary external fixator is easy to operate; the surgical procedure is simple and time-saving for surgeon when 3D modeling is unavailable. The indication for temporary external fixator usage is the mandibular lesion growing outward to cheek soft tissue.

Systemic miRNA delivery by nontoxic nanoscale coordination polymers limits epithelial-to-mesenchymal transition and suppresses liver metastases of colorectal cancer.

Though early detection and treatment of primary tumors has significantly improved in recent years, metastatic disease remains among the most significant challenges in cancer therapy. Cancer cells can disseminate before the primary tumor is detected to form micro or gross metastases, requiring toxic systemic therapies. To prevent and suppress metastases, we have developed a nontoxic, long-circulating nanoscale coordination polymer (NCP) protecting microRNA (miRNA) in circulation and releasing it in tumors. PtIV(en)2 [en = ethylenediamine] containing NCPs (PtEN) can release a nontoxic, kinetically inert PtII(en)2 compound and carbon dioxide which aids the endosomal escape of its miRNA cargo, miR-655-3p. Without the presence of the PtEN core, the miRNA showed cellular uptake but no effect. When transfected into human colorectal HCT116 cells by NCPs, this oligometastatic miRNA limited proliferation and epithelial-to-mesenchymal transition by preventing ß-catenin nuclear translocation and tumor cell invasion. Systemic administrations of PtEN/miR-655-3p sustained effective transfection to reduce liver colonization and tumor burden in a xenogenic hepatic metastatic model of HCT116 without any observable toxicity.

Author Correction: Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis.

In the originally published version of this Article, the affiliation details for Kevin P. White inadvertently omitted 'Tempus Labs, Chicago, IL, 60654, USA'. This has now been corrected in both the PDF and HTML versions of the Article.

[Clinical treatment and prognosis of 52 cases of neurinoma in parotid region].

PURPOSE: To investigate the clinical features, diagnosis, and treatment, as well as prognosis of neurinoma in parotid region, in order to provide references for clinical treatment. METHODS: Fifty-two cases of neurinoma in parotid region treated between June 2000 to December 2013 were retrospectively investigated, including their clinical characteristics, imaging examination, diagnosis, therapies and prognosis. SPSS13.0 software package was used for Fisher's exact test. RESULTS: Nine cases (17.31%) in all had facial paralysis, discomfort and other neural symptoms before operation. Eleven cases(21.15%) was preoperatively diagnosed. All patients were treated with surgery, pathologically diagnosed and followed up for 42 months to 206 months. No recurrence and malignant transformation were found. Twenty-eight cases (53.85%) had symptoms of facial nerve injury postoperatively, but 18 cases (64.29%) were improved functionally. When there was no obvious correlation between the tumor and facial nerve, no facial nerve paralysis was found. When the tumor was located on the facial nerve, the rate of preserving facial nerve function was 22.22%, the rate of intracapsular enucleation of the neurinoma was 85.71%, and the effective rate of excision followed by facial nerve reconstruction was 85.71%. CONCLUSIONS: The diagnosis of neurinoma in parotid region is difficult and needed to be confirmed by postoperative pathology. The preservation of facial nerve function should be the utmost procedure during operation while intracapsular enucleation is the first choice. However, in order to restore the function of facial nerve, nerve reconstruction should be performed as soon as possible.