Tislelizumab, a novel PD-1 monoclonal antibody in urothelial cancer: A real-world study.

OBJECTIVE: Tislelizumab, a monoclonal antibody against programed death protein-1 (PD-1), has shown encouraging antitumor activity in urothelial cancer. This study was designed to assess the efficacy and safety of tislelizumab in urotelial cancer in a real-world setting. METHODS: The study was a real-world retrospective study undertaken at Liaoning Cancer Hospital & Institute, China. Eligible patients were ≥18 years. Patients received 200-mg tislelizumab monotherapy intravenously every 3 weeks until the disease progressed to intolerable toxicity. Outcomes included an objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Between March 2020 and December 2022, 33 patients were enrolled. The median follow-up was 10.17 (IQR 5.73-12.47) months. Of all 33 patients, ORR and DCR were 30.30% (95% CI 15.6%-48.7%) and 42.42% (95% CI 25.48%-60.78%), respectively. The median PFS was 5.73 (95% CI 3.27-13.00) months, with a 12-month PFS rate of 31.90% (95% CI 19.20%-53.00%). The median OS was 17.7 (95% CI 12.80-not reach) months, with a 12-month OS rate of 67.50% (95% CI 52.70%-86.40%). Eleven (33.33%) and 8 (24.24%) experienced ≥grade 3 treatment-related adverse events (TRAEs) and immune-related Aes, respectively. No treatment-related deaths occurred. CONCLUSION: The excellent efficacy and controllable safety of tislelizumab in locally advanced or metastatic urothelial cancer suggest that it may be a promising therapeutic option for this population.

[Differences in clinicopathological features, gene mutations, and prognosis between primary gastric and intestinal gastrointestinal stromal tumors in 1061 patients].

Objective: To analyze the clinicopathological features and gene mutations of primary gastrointestinal stromal tumors (GISTs) of the stomach and intestine and the prognosis of intermediate- and high-risk GISTs. Methods: This was a retrospective cohort study. Data of patients with GISTs admitted to Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019 were collected retrospectively. Patients with primary gastric or intestinal disease who had undergone endoscopic or surgical resection of the primary lesion and were confirmed pathologically as GIST were included. Patients treated with targeted therapy preoperatively were excluded. The above criteria were met by 1061 patients with primary GISTs, 794 of whom had gastric GISTs and 267 intestinal GISTs. Genetic testing had been performed in 360 of these patients since implementation of Sanger sequencing in our hospital in October 2014. Gene mutations in KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were detected by Sanger sequencing. The factors investigated in this study included: (1) clinicopathological data, such as sex, age, primary tumor location, maximum tumor diameter, histological type, mitotic index (/5 mm2), and risk classification; (2) gene mutation; (3) follow-up, survival, and postoperative treatment; and (4) prognostic factors of progression-free survival (PFS) and overall survival (OS) for intermediate- and high-risk GIST. Results: (1) Clinicopathological features: The median ages of patients with primary gastric and intestinal GIST were 61 (8-85) years and 60 (26-80) years, respectively; The median maximum tumor diameters were 4.0 (0.3-32.0) cm and 6.0 (0.3-35.0) cm, respectively; The median mitotic indexes were 3 (0-113)/5 mm² and 3 (0-50)/5 mm², respectively; The median Ki-67 proliferation indexes were 5% (1%-80%) and 5% (1%-50%), respectively. The rates of positivity for CD117, DOG-1, and CD34 were 99.7% (792/794), 99.9% (731/732), 95.6% (753/788), and 100.0% (267/267), 100.0% (238/238), 61.5% (163/265), respectively. There were higher proportions of male patients (χ²=6.390, P=0.011), tumors of maximum diameter > 5.0 cm (χ²=33.593, P<0.001), high-risk (χ²=94.957, P<0.001), and CD34-negativity (χ²=203.138, P<0.001) among patients with intestinal GISTs than among those with gastric GISTs. (2) Gene mutations: Gene mutations were investigated in 286/360 patients (79.4%) with primary gastric GISTs and 74/360 (20.6%) with primary intestinal GISTs. Among the 286 patients with gastric primary GISTs, 79.4% (227/286), 8.4% (24/286), and 12.2% (35/286), had KIT mutations, PDGFRA mutations, and wild-type, respectively. Among the 74 patients with primary intestinal GISTs, 85.1% (63/74) had KIT mutations and 14.9% (11/74) were wild-type. The PDGFRA mutation rate was lower in patients with intestinal GISTs than in those with gastric GISTs[ 0% vs. 8.4%(24/286), χ²=6.770, P=0.034], whereas KIT exon 9 mutations occurred more often in those with intestinal GISTs [22.2% (14/63) vs. 1.8% (4/227), P<0.001]. There were no significant differences between gastric and intestinal GISTs in the rates of KIT exon 11 mutation type and KIT exon 11 deletion mutation type (both P>0.05). (3) Follow-up, survival, and postoperative treatment: After excluding 228 patients with synchronous and metachronous other malignant tumors, the remaining 833 patients were followed up for 6-124 (median 53) months with a follow-up rate of 88.6% (738/833). None of the patients with very low or low-risk gastric (n=239) or intestinal GISTs (n=56) had received targeted therapy postoperatively. Among 179 patients with moderate-risk GISTs, postoperative targeted therapy had been administered to 88/155 with gastric and 11/24 with intestinal GISTs. Among 264 patients with high-risk GISTs, postoperative targeted therapy had been administered to 106/153 with gastric and 62/111 with intestinal GISTs. The 3-, 5-, and 10-year PFS of patients with gastric or intestinal GISTs were 96.5%, 93.8%, and 87.6% and 85.7%, 80.1% and 63.3%, respectively (P<0.001). The 3-, 5-, and 10-year OS were 99.2%, 98.8%, 97.5% and 94.8%, 92.1%, 85.0%, respectively (P<0.001). (4) Analysis of predictors of intermediate- and high-risk GISTs: The 5-year PFS of patients with gastric and intestinal GISTs were 89.5% and 73.2%, respectively (P<0.001); The 5-year OS were 97.9% and 89.3%, respectively (P<0.001). Multivariate analysis showed that high risk (HR=2.918, 95%CI: 1.076-7.911, P=0.035) and Ki-67 proliferation index > 5% (HR=2.778, 95%CI: 1.389-5.558, P=0.004) were independent risk factors for PFS in patients with intermediate- and high-risk GISTs (both P<0.05). Intestinal GISTs (HR=3.485, 95%CI: 1.407-8.634, P=0.007) and high risk (HR=3.753,95%CI:1.079-13.056, P=0.038) were independent risk factors for OS in patients with intermediate- and high-risk GISTs (both P<0.05). Postoperative targeted therapy was independent protective factor for PFS and OS (HR=0.103, 95%CI: 0.049-0.213, P<0.001; HR=0.210, 95%CI:0.078-0.564,P=0.002). Conclusions: Primary intestinal GIST behaves more aggressively than gastric GISTs and more frequently progress after surgery. Moreover, CD34 negativity and KIT exon 9 mutations occur more frequently in patients with intestinal GISTs than in those with gastric GISTs.

Microsurgical approach for resection of the filum terminale internum in tethered cord syndrome-a case demonstration of technical nuances and vignettes.

BACKGROUND: In tethered cord syndrome due to filum terminale pathology, the surgical approach to achieve detethering of the spinal cord may vary. Traditionally, sectioning the filum through a laminectomy at the lumbosacral level is performed. METHOD: A microsurgical technique at a higher level to approach the filum below the conus tip is performed. This allows for removal of the entire distal portion of the filum through a limited interlaminar approach and dural opening. CONCLUSION: We propose a technique to transect the filum terminale below the conus tip and extract the distal filum by releasing it from its intradural attachments to minimize any remnants of the filum terminale.

Superficial temporal artery injury and delayed post-cranioplasty infection.

OBJECTIVE: Complications after cranioplasty after decompressive craniectomy (DC) have been reported to be as high as 40%. The superficial temporal artery (STA) is at substantial risk for injury in standard reverse question-mark incisions that are typically used for unilateral DC. The authors hypothesize that STA injury during craniectomy predisposes patients to post-cranioplasty surgical site infection (SSI) and/or wound complication. METHODS: A retrospective study of all patients at a single institution who underwent cranioplasty after decompressive craniectomy and who underwent imaging of the head (computed tomography angiogram, magnetic resonance imaging with intravenous contrast, or diagnostic cerebral angiography) for any indication between the two procedures was undertaken. The degree of STA injury was classified and univariate statistics were used to compare groups. RESULTS: Fifty-four patients met inclusion criteria. Thirty-three patients (61%) had evidence of complete or partial STA injury on pre-cranioplasty imaging. Nine patients (16.7%) developed either an SSI or wound complication after cranioplasty and, among these, four (7.4%) experienced delayed (>2 weeks from cranioplasty) complications. Seven of 9 patients required surgical debridement and cranioplasty explant. There was a stepwise but non-significant increase in post-cranioplasty SSI (STA present: 10%, STA partial injury: 17%, STA complete injury: 24%, P=0.53) and delayed post-cranioplasty SSI (STA present: 0%, STA partial injury: 8%, STA complete injury: 14%, P=0.26). CONCLUSIONS: There is a notable but statistically non-significant trend toward increased rates of SSI in patients with complete or partial STA injury during craniectomy.

[Effects of cinepazide maleate injection on blood pressure in patients with acute ischemic stroke and hypertension].

Objective: To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection. Methods: This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes. Results: This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%,P>0.05) between cinepazide maleate group and control group. Conclusion: Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

CBD Promotes Oral Ulcer Healing via Inhibiting CMPK2-Mediated Inflammasome.

Oral ulcer is a common oral inflammatory lesion accompanied by severe pain but with few effective treatments. Cannabidiol (CBD) is recently emerging for its therapeutic potential in a range of diseases, including inflammatory conditions and cancers. Here we show that CBD oral spray on acid- or trauma-induced oral ulcers on mice tongue inhibits inflammation, relieves pain, and accelerates lesion closure. Notably, the enrichment of genes associated with the NOD, LRR, and NLRP3 pyrin domain-containing protein 3 (NLRP3) inflammasome pathway is downregulated after CBD treatment. The expression of cleaved-gasdermin D (GSDMD) and the percentage of pyroptotic cells are reduced as well. In addition, CBD decreases the expression of cytidine/uridine monophosphate kinase 2 (CMPK2), which subsequently inhibits the generation of oxidized mitochondria DNA and suppresses inflammasome activation. These immunomodulating effects of CBD are mostly blocked by peroxisome proliferator activated receptor γ (PPARγ) antagonist and partially antagonized by CB1 receptor antagonist. Our results demonstrate that CBD accelerates oral ulcer healing by inhibiting CMPK2-mediated NLRP3 inflammasome activation and pyroptosis, which are mediated mostly by PPARγ in the nucleus and partially by CB1 in the plasma membrane.

Diagnostic magnetic resonance imaging in synovial chondromatosis of the temporomandibular joint.

The aim of this paper was to investigate the clinical and magnetic resonance imaging (MRI) features of synovial chondromatosis (SC) of the temporomandibular joint (TMJ). Fourteen patients with SC of the TMJ were included in the study. Clinical and MRI features were analysed and divided into three types based on MRI classification: type I with loose bodies, type II with homogeneous masses, and type III with a mixture of loose bodies and homogeneous masses. All SCs occurred in the superior compartment of the TMJ. There were two patients (14%) categorised as type I, five (36%) as type II and seven (50%) as type III. Four patients (29%) had disc perforation, and nine had bone erosion; among those nine, seven (78%) had type III and two (22%) type II. Histological examination showed inflammation and calcification in the synovial membrane and, and cartilage of the hyaline type in all cases. MRI has advantages in the diagnosis of SC.

[Association of status of mismatch repair protein expression and EB virus infection with clinicopathological parameters in 886 gastric adenocarcinoma patients].

Objective: To analyze the expression of mismatch repair (MMR) protein and the EB virus infection in gastric adenocarcinoma, and to examine the association of MMR expression and EB virus infection with clinicopathological parameters. Methods: A case-control study was performed. Clinicopathological data of patients who was pathologically diagnosed as gastric adenocarcinoma, received radical gastrectomy and had complete clinicopathological data from August 2017 to April 2020 in Tianjin Medical University Cancer Institute and Hospital were retrospectively collected and analyzed. The immunohistochemistry (IHC) of MMR proteins and in situ hybridization (ISH) of Epstein-Barr virus encoded RNA (EBER) were reviewed. The associations of MMR and EBER results with clinicopathological parameters were analyzed. The main observations of the study were MMR and EBER expression, and association of MMR and EBER results with clinicopathological parameters. Results: Eight hundred and eighty-six patients were enrolled, including 98 patients who received preoperative neoadjuvant chemoradiotherapy. Of 886 patients, 613 (69.2%) were males and the median age was 60 (22-83) years; 831 (93.8%) were mismatch repair proficiency (pMMR), and 55 (6.2%) were mismatch repair deficiency (dMMR). In dMMR group, 47 cases (85.5%) had the deficiency of both MLH1 and PMS2, 1 case (1.8%) had the deficiency of both MSH2 and MSH6, 4 cases (7.3%) had the deficiency only in PMS2, 2 cases (3.6%) had the deficiency only in MSH6, and 1 case (1.8%) had the deficiency only in MSH2. The deficiency rates of PMS2, MLH1, MSH6 and MSH2 were 5.8% (51/886), 5.3% (47/886), 0.3% (3/886) and 0.2% (2/886), respectively. Among the 871 cases with EBER results, 4.9% (43/871) were positive EBER. Univariate analysis showed that dMMR was more frequently detected in female patients (χ(2)=10.962, P=0.001), cancer locating in the antrum (χ(2)=9.336,P=0.020), Lauren intestinal type (χ(2)=9.718, P=0.018), stage T3 (χ(2)=25.866, P<0.001) and TNM stage II (χ(2)=15.470, P=0.002). The ratio of dMMR was not significantly associated with age, tumor differentiation, histological type, lymph node metastasis, distant metastasis or Her-2 immunohistochemical score (all P>0.05). Compared with negative EBER, positive EBER was more frequent in male patients (χ(2)=9.701, P=0.002), cancer locating in gastric fundus and corpus (χ(2)=17.964, P<0.001), gastric cancer with lymphoid stroma (χ(2)=744.073, P<0.001) and poorly differentiated cancer (χ(2)=13.739, P=0.010). Positive EBER was not significantly associated with age, depth of invasion, lymph node metastasis, distant metastasis, TNM stage or Her-2 immunohistochemical score (all P>0.05). In addition, all dMMR cases were EBER negative, and all cases of positive EBER were pMMR. Conclusions: The positive EB virus status is mutually exclusive with dMMR, indicating that different molecular subtypes of gastric adenocarcinoma are involved in different molecular pathways in tumorigenesis and progression. The overlapping of dMMR or positive EBER status and positive Her-2 expression is found in some cases of gastric adenocarcinoma. Patients with gastric adenocarcinoma after radical surgery should be tested for MMR status if they are female, the tumor locates in gastric antrum, the TNM staging is stage II or T3, or if the Lauren classification is intestinal type. And if patients are male, the tumor locates in the gastric fundus and corpus, the cancer is lymphoid stroma, or poor differentiated, the expression of EBER should be detected. Results of our study may provide evidence for further decision-making of clinical treatment.

[Mismatch repair protein expression of colorectal cancer: a retrospective analysis of 3 428 cases].

Objective: To analyze the expression of mismatch repair (MMR) proteins in colorectal cancers (CRC) and to evaluate the feasibility and potential pitfalls of immunohistochemistry (IHC) analysis for MMR. Methods: The IHC sections for MMR proteins were reviewed in 3 428 cases of resected CRC without neoadjuvant therapy at Tianjin Medical University Cancer Institute and Hospital from July 2014 to October 2018. For the cases with unclear MMR IHC results during the initial review, IHC staining was repeated and microsatellite instability (MSI) analysis was performed. Relationships between the expression of MMR proteins and MSI status as well as the clinicopathological parameters were analyzed. Results: IHC staining for MMR was repeated in 28 (0.8%) cases due to poor quality of original IHC sections. Inconsistent results between the original diagnosis and re-diagnosis were found in 119 (3.5%) cases, mainly resulting from PMS2 and MLH1. Finally, 261 (7.6%) cases of CRC showed mismatch repair deficiency (dMMR), mainly from the deficiency of both MLH1 and PMS2 (43.3%,113/261). In the 14 cases with MSI results, the concordant of MSI and MMR was 13 cases. In the 29 dMMR cases with next generation sequencing (NGS) results, the concordant of MSI-high and dMMR was 93.1%(27/29). The cases with inconsistent results between MSI and MMR showed negative expression of MSH6 or PMS2. Twenty-one CRC showed negative expression of MLH1 and partially positive (or weak positive) expression of PMS2, or negative expression of MSH2 and partially positive (or weak positive) expression of MSH6. Among the 19 cases with MSI results, 16 cases were MSI-high, two cases were MSI-low, and one case was microsatellite stable. Compared with mismatch repair proficiency (pMMR), dMMR was more frequently detected in female patients younger than 50 years old, with family history, at early stage (Ⅰ-Ⅱ) CRC, and in the tumors from right colon,with poor differentiation, or mucinous adenocarcinoma/signet ring cell carcinoma (all P<0.05). Conclusions: At present, IHC staining is a clinically effective and convenient method to detect MMR expression, but the operating process and result assessment remain variable and need to be standardized. MSI analysis can be performed in the difficult-to-evaluate cases for MMR to enhance prognostic evaluation and treatment option.

Manipulation of the two-site Kondo effect in linear CoCu n CoCu m clusters.

Artificially assembled linear atomic clusters, CoCu n CoCu m , are used to explore variations of the Kondo effect at the two Co sites. For all investigated Cu n chain lengths ([Formula: see text]) the addition of a single Cu atom to one edge Co atom of the chain ([Formula: see text]) strongly reduces the amplitude of the Abrikosov-Suhl-Kondo resonance of that Co atom. Concomitantly, the resonance line width is more than halved. On the contrary, the Kondo effect of the opposite edge Co atom remains unaffected. Hybridization together with the linear geometry of the cluster are likely to drive the effect.

Periodontal pathogens and clinical parameters in chronic periodontitis.

The use of next generation sequencing and bioinformatics has revealed the complexity and richness of the human oral microbiota. While some species are well known for their periodontal pathogenicity, the molecular-based approaches for bacterial identification have raised awareness about new putative periodontal pathogens. Although they are found increased in case of periodontitis, there is currently a lack of data on their interrelationship with the periodontal measures. We processed the sequencing data of the subgingival microbiota of 75 patients with hemochromatosis and chronic periodontitis in order to characterize the well-described and newly identified subgingival periodontal pathogens. We used correlation tests and statistical models to assess the association between the periodontal pathogens and mean pocket depth, and to determine the most relevant bacterial biomarkers of periodontitis severity. Based on correlation test results, nine taxa were selected and included in the statistical models. The multiple linear regression models adjusted for systemic and periodontal clinical variables showed that mean pocket depth was negatively associated with Aggregatibacter and Rothia, and positively associated with Porphyromonas. Furthermore, a bacterial ratio that was previously described as a signature of dysbiosis in periodontitis (%Porphyromonas+%Treponema+%Tannerella)/(%Rothia+%Corynebacterium) was the most significant predictor. In this specific population, we found that the best model in predicting the mean pocket depth was microbial dysbiosis using the dysbiosis ratio taxa formula. While further studies are needed to assess the validity of these results on the general population, such a dysbiosis ratio could be used in the future to monitor the subgingival microbiota.

[Analysis of differences in epidemiology and clinical features of Guillain-Barré syndrome between rural and urban areas of southern China].

Objective: To explore the differences in epidemiology and clinical features of Guillain- Barré syndrome (GBS) between rural and urban areas of southern China. Methods: The clinical data of 759 hospitalized GBS patients from 31 hospitals of 13 provinces/cities in southern China, between January 1st, 2013 and September 30th, 2016, were collected and analyzed retrospectively. Results: The risk of GBS was higher for males than females in rural and urban areas and the median age was 49 and 48 years, respectively. Seasonal clustering in winter and spring was noted in both rural and urban areas, and the seasonal trend was more markedly in rural areas, but the differences showed no statistical significance. There were 70.37% of patients in rural areas and 73.69% in urban areas who had antecedent respiratory infection. The median time from onset to nadir was 7 days, and Hughes Disability Scale at admission, nadir and discharge were (2.95±1.10 vs 2.84±1.15), (3.25±1.11 vs 3.14±1.21), (2.02±1.24 vs 2.00±1.31) in rural and urban areas respectively. Albuminocytologic dissociation was present in 84.34% of patients in rural areas and 84.62% of cases in urban areas. There were 8.65% and 10.94% of cases in rural and urban areas who required mechanical ventilation during hospitalization, respectively. Demyelinating GBS accounted for 53.29% and 48.77%, respectively, in patients with findings of nerve conduction studies available in rural and urban areas. Conclusions: GBS in rural areas of southern China showed male predominance and a peak of spring and winter occurrence, with respiratory infection as the predominated preceding events and demyelinating GBS being main clinical subtype. Winter and spring showed a higher incidence of GBS in rural and urban areas. There were no significant differences of sex, age, preceding events, season trend, progression of disease, clinical subtypes and cerebrospinal fluid investigations in GBS patients between rural and urban areas.

The Effect of Interleukin 38 on Inflammation-induced Corneal Neovascularization.

BACKGROUND: Angiogenesis is tightly linked to inflammation. Cytokines of interleukin 1 (IL-1) family are key mediators in modulating inflammatory responses. METHODS: In this study, we examined the role of IL-38, a member of the IL-1 family, in mediating inflammation-induced angiogenesis. RESULTS: The results showed that the angiogenesis was attenuated by topical administration of IL-38 to the injured corneas in a mouse model of alkali-induced corneal neovascularization (CNV). Further study showed that the expression of inflammatory cytokines TNF-α, IL-6, IL-8 and IL-1ß was decreased in the IL-38-treated corneas. Moreover, the angiogenic activities including the proliferation, migration and tube formation of human retinal endothelial cells were reduced by IL-38 treatment in vitro. CONCLUSION: The data indicate that IL-38 modulates inflammation-induced angiogenesis.

[The effects of silica dust on the expression of MyD88 and TRAF6 mRNA of lung macrophages in rats].

Objective: To investigate the effects of silica dust on the expression of Myeloid differentiation factor 88 (MyD88) mRNA and tumor necrosis factor receptor-associated factor (TRAF6) mRNA of lung macrophages in rats. Methods: Selecting 40 SPF-class Wistar rats with average weight (200±20) g randomly divided into control group and 30 d, 60 d, 120 d experimental groups with 10 rats in each group according to body weight. The experimental groups rats were injected with 1 ml of SiO(2) (100 mg/ml) suspension through the trachea into lung only once, then they were respectively killed after 30, 60, 120 days. The control group rats were injected with 1 ml of saline into lung, and killed after 120 days. The lungs of the rats were taken for pathological observation. Lung macrophages were extracted and counted, and their activity was detected by MTT. RT-qPCR was used to assess the relative contents of MyD88 mRNA and TRAF6 mRNA. Results: Silica dust inhalation led to infiltration of lung tissue cells, thickening the alveolar wall and destruction of alveolar structure. The longer the exposure to dust, the more obvious the results were. The number of macrophages in all experimental groups and activity in the 30 d, 60 d groups were significantly higher than that in the control group (P<0.05) . Among them, 30 d group had the largest number and the highest activity. Compared with the control group, the expression of MyD88 mRNA and TRAF6 mRNA of lung macrophages in rats increased in the experimental groups (P<0.05) , especially in the 60 d group. Conclusion: Silica dust inhalation can increase the expression of MyD88 and TRAF6 in macrophages, suggesting that silica dust can induce silicosis fibrosis by activating TLR/NF-κB signal pathway.

Systematic analyses for candidate genes of milk production traits in water buffalo (Bubalus Bubalis).

Water buffalo (Bubalus bubalis) is of great economic importance as a provider of milk and meat in many countries. However, the milk yield of buffalo is much lower than that of Holstein cows. Selection of candidate genes related to milk production traits can be applied to improve buffalo milk performance. A systematic review of studies of these candidate genes will be greatly beneficial for researchers to timely and efficiently understand the research development of molecular markers for buffalo milk production traits. Here, we identified and classified the candidate genes associated with buffalo milk production traits. A total of 517 candidate genes have been identified as being associated with milk performance in different buffalo breeds. Nineteen candidate genes containing 47 mutation sites have been identified using the candidate gene approach. In addition, 499 candidate genes have been identified in six genome-wide association studies (GWASes) including two studies performed with the bovine SNP chip and four studies with the buffalo SNP chip. Genes CTNND2 (catenin delta 2), APOB (apolipoprotein B), FHIT (fragile histidine triad) and ESRRG (estrogen related receptor gamma) were identified in at least two GWASes. These four genes, especially APOB, deserve further study to explore regulatory roles in buffalo milk production. With growth in the number of buffalo genomic studies, more candidate genes associated with buffalo milk production traits will be identified. Therefore, future studies, such as those investigating gene location and functional analyses, are necessary to facilitate the exploitation of genetic potential and the improvement of buffalo milk performance.

[Application of mixed reality real-time navigation combined with 3D visualization in complicated hepatectomy].

Objective: To explore the application value of mixed-reality (MR) navigation combined with three-dimensional visualization technique in complicated hepatectomy. Methods: A retrospective analysis of the clinical data of fifty patients with complex liver cancer who underwent liver resection in the Department of hepatobiliary surgery of Nantong Tumor Hospital during September 2015 to October 2017 was conducted. These patients were randomly divided into control group and experimental group, including 22 cases in the experimental group, using three-dimensional visualization technique for preoperative assessment, and MR surgery intraoperative navigation technology, and 28 cases in the control group, in which the three-dimensional visualization technique and the MR navigation were not performed. The surgeons of the two groups were the same. The preoperative, intraoperative and postoperative indexes of the two groups were compared and analyzed. Results: There was no significant difference in preoperative indexes. But in the intraoperative indexes, the operation time [(82.3±10.4) min vs (96.6±22.7) min] and hepatic portal blocking time [(12.2±3.8) min VS (15.8±4.2) min] of the experimental group were significantly shorter than those of the control group, meanwhile, the amount of intraoperative bleeding [(486.4±118.5) ml vs (567.2±142.8) ml] and the volume of intraoperative blood transfusion of [(1.8±0.2) U vs (2.5±0.6) U] were significantly decreased. These differences were statistically significant. In the postoperatively, the total incidence of postoperative complications (4/22 vs 13/28) of the experimental group was lower than that of the control group, and the difference was statistically significant. Conclusion: In complicated hepatectomy, MR intraoperative navigation combined with three-dimensional visualization technique which used for preoperative assessment can significantly shorten operation time, hepatic portal blocking time, significantly reduce intraoperative blood loss and transfusion volume, and significantly reduce the incidence of postoperative total complications, which is of clinical value.

Immunoexpression of aquaporins 1, 2, 3 and 4 in kidney of yak (Bos grunniens) on the Qinghai-Tibetan Plateau.

Aquaporins (AQP) 1, 2, 3 and 4 belong to the aquaporin water channel family and play an important role in urine concentration by reabsorption of water from renal tubule fluid. Renal AQPs have not been reported in the yak (Bos grunniens), which resides in the Qinghai Tibetan Plateau. We investigated AQPs 1-4 expressions in the kidneys of Yak using immunohistochemical staining. AQP1 was expressed mainly in the basolateral and apical membranes of the proximal tubules and descending thin limb of the loop of Henle. AQP2 was detected in the apical plasma membranes of collecting ducts and distal convoluted tubules. AQP3 was located in the proximal tubule, distal tubule and collecting ducts. AQP4 was located in the collecting ducts, distal straight tubule, glomerular capillaries and peritubular capillaries. The expression pattern of AQPs 1-4 in kidney of yak was different from other species, which possibly is related to kidney function in a high altitude environment.

[The role of prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in breast cancer receiving adjuvant chemotherapy].

Objectives: To investigate the efficacy and safety of prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in breast cancer receiving docetaxel as adjuvant chemotherapy. Methods: A total of 58 patients with breast cancer receiving adjuvant chemotherapy with docetaxel were included between January 2014 to October 2017. Prophylactic use of PEG-rhG-CSF was administered.Patients were further divided into two groups according to the frequency of PEG-rhG-CSF use: frequent use group (≥3 cycles) and non-frequent use group (<3 cycles). Results: There were significant differences in the incidence rates of grade 3/4 neutropenia between the prophylactic group and non-prophylactic group in cycle 1-3(P<0.05). Less febrile neutropenia (FN) was also noted in the prophylactic group compared with the non-prophylactic group in cycle 1 and cycle 3 (P<0.05). Grade 3/4 neutropenia and FN were less in the frequent use of group compared with the non-frequent use group(P<0.001). The most common side effects of PEG-rhG-CSF included fatigue (10.2%), bone joint pain(50.8%), and 2 patients (3.4%) refused further treatment because of bone joint pain. Conclusions: PEG-rhG-CSF should be prophylactically used for preventing neutropenia and febrile neutropenia in breast cancer patients receiving adjuvant chemotherapy with docetaxel regimen.

Correlation between coronary artery lesion quantitative score and OSAHS and relative risk factors.

OBJECTIVE: The purpose of this study was to investigate the relationship of obstructive sleep apnea hypopnea syndrome (OSAHS) with coronary artery lesion quantitative score Syntax Score (SX score) and risk factors for coronary heart disease (CHD). PATIENTS AND METHODS: A total of 115 patients with OSAHS admitted to the Department of Cardiology in our hospital from January 2011 to June 2015 were selected. Philips Respironics Alice 5 Polysomnography was used for sleep monitoring. The patients were divided into mild group (n=32), moderate group (n=36) and severe group (n=47) according to apnea hypopnea index (AHI). Coronary angiography was performed for the patients, and SX score was calculated. Fasting venous blood was extracted from all patients with OSAHS and sent for detection of blood routine, coagulation, liver and kidney function, blood lipid and other indexes, and all patients received color Doppler echocardiography. RESULTS: The body weight and body mass index (BMI) of patients with OSAHS in severe group were higher than those in the mild group and moderate group (p<0.05). The content of fibrinogen (FIB) of patients in severe group was higher than that in mild group (p<0.01). The levels of total cholesterol (TC) (p<0.05), blood uric acid (p<0.05), and serum creatinine (p<0.01) of patients in the severe group were significantly higher than those in mild group and moderate group, but there were no differences between mild group and moderate group (p>0.05). Echocardiography suggested that the left atrium diameter 1 (LAD) and pulmonary artery pressure (PAP) of patients in severe group were larger than those in the mild group and moderate group (p<0.01), and the right ventricle anteroposterior diameter (RVD) in the mild group was smaller than those in the moderate group (p<0.05) and severe group (p<0.01). The score of patients with OSAHS in the severe group was higher than those in the mild group and moderate group (p<0.01), and SX score was increased with AHI (r=0.416, p<0.01). Logistic regression analysis showed that AHI and SX score could not be used as indicators to judge the prognosis of patients. CONCLUSIONS: There is a positive correlation between AHI and SX score in patients with OSAHS, indicating that with the aggravation of respiratory sleep disorder, SX score is increased significantly and the severity of coronary artery lesion is increased accordingly.