[Efficacy of neoadjuvant therapy on HER2-positive breast cancer: a clinicopathological analysis].

Objective: To investigate the efficacy of neoadjuvant therapy (NAT) on HER2-positive breast cancer and to analyze their clinicopathological features. Methods: A total of 480 cases of HER2-positive breast cancer who received neoadjuvant therapy (NAT), diagnosed at the Department of Pathology of Fudan University Shanghai Cancer Center from 2015 to 2020, were retrospectively identified. Clinicopathological parameters such as age, tumor size, molecular subtype, type of targeted therapy, Ki-67 proliferation index, ER and HER2 immunohistochemical expression, and HER2 amplification status were analyzed to correlate with the efficacy of NAT. Results: Among 480 patients with HER2-positive breast cancer, 209 achieved pathology complete response (pCR) after NAT, with a pCR rate of 43.5%. Of all the cases,457 patients received chemotherapy plus trastuzumab and 23 patients received chemotherapy with trastuzumab and pertuzumab. A total of 198 cases (43.3%) achieved pCR in patients with chemotherapy plus trastuzumab, and 11 cases (47.8%) achieved pCR in patients with chemotherapy plus trastuzumab and pertuzumab. The pCR rate in the latter group was higher, but there was no statistical significance. The results showed that the pCR rate of IHC-HER2 3+patients (49%) was significantly higher than that of IHC-HER2 2+patients (26.1%, P<0.001). The higher the mean HER2 copy number in the FISH assay, the higher the pCR rate was achieved. The expression level of ER was inversely correlated with the efficacy of NAT, and the pCR rate in the ER-positive group (28.2%) was significantly lower than that in the ER-negative group (55.8%, P<0.001). The pCR rate (29.1%) of patients with luminal B type was lower than that of HER2 overexpression type (55.8%, P<0.001). In addition, higher Ki-67 proliferation index was associated with higher pCR rate (P<0.001). The pCR rate was the highest in the tumor ≤2 cm group (57.7%), while the pCR rate in the tumor >5 cm group was the lowest (31.1%). The difference between the groups was significant (P=0.005). Conclusions: HER2 copy numbers, HER2 immunohistochemical expression level, molecular subtype, ER expression level and Ki-67 proliferation index are significantly associated with pCR after NAT. In addition, fluorescence in situ hybridization results, HER2/CEP17 ratio and tumor size could also significantly affect the efficacy of NAT.

[Correlation between serum autotaxin level and pulmonary ultrasound score with the disease severity and 28-day mortality in patients with acute respiratory disease syndrome].

Objective: To investigate the relationship between serum autocrine motor factor (Autotaxin) level and pulmonary ultrasound score (LUS) and the disease severity and 28-day mortality of patients with acute respiratory distress syndrome (ARDS). Methods: Totally 142 ARDS patients admitted to Danzhou People's Hospital from January 2019 to December 2021 were selected, and serum Autotaxin level and LUS score of ARDS patients on the day of onset were detected. According to the survival within 28 days after entering the intensive care unit, ARDS patients were divided into survival group (86 cases) and death group (56 cases). According to the oxygenation index, ARDS patients were divided into mild group (200 mmHg

[Long-term prevention and control effects of orthokeratology lenses designed for small treatment zones on children and adolescents with myopia].

Objective: To explore the characteristics of orthokeratology lenses designed for small correction zones and their effectiveness and safety in long-term prevention and control of myopia in children and adolescents. Methods: It was a prospective cohort study that included myopic children and adolescents who received corneal reshaping treatment at the Qingdao Eye Hospital of Shandong First Medical University between January 2019 and May 2020. The patients were randomly divided into two groups using computer-generated randomization, and were fitted with corneal reshaping lenses with small treatment zones and conventional designs, respectively. The uncorrected visual acuity, best-corrected visual acuity, refractive error, and axial length were measured before and after 6, 12, and 18 months of wearing the lenses. Corneal topography with the Pentacam was also performed, and the area and diameter of the corneal treatment zone were calculated using the Matlab software. Results: A total of 60 myopic patients (60 eyes) were enrolled, including 29 males and 31 females, with an age of (10.40±1.01) years and a spherical equivalent of (-2.88±0.42) D. There were 30 cases in the small correction zone group and 30 cases in the conventional group. There was no significant difference in uncorrected visual acuity and spherical equivalent between the two groups at each time point after treatment. The axial growth in the conventional group was (0.16±0.09) mm at 6 months after treatment, (0.28±0.17) mm at 12 months, and (0.37±0.20) mm at 18 months, whereas in the small treatment zone group it was (0.06±0.05) mm, (0.12±0.10) mm, and (0.18±0.14) mm, respectively. The myopia progression rate in the small treatment zone group was only 37.50%, 42.86%, and 48.64% of the conventional group at 6, 12, and 18 months, respectively. Corneal topography showed that the treatment area in the conventional group was (6.98±0.89) mm², while in the small treatment zone group it decreased by 23.2% [(5.36±0.73) mm²] (P<0.05). Correlation analysis revealed that the axial increase after 18 months of lens wearing was negatively correlated with the age before lens wearing (P<0.05), positively correlated with the corneal surface treatment zone size (P<0.05), and not correlated with the pupil diameter and spherical equivalent (all P>0.05). After the shaping treatment, the rate of adverse reaction, which was mild, in both groups was 10%, and the symptoms disappeared. Conclusion: Orthokeratology lenses with smaller treatment zones can significantly reduce the rate of axial length growth in children and adolescents compared to lenses with conventional treatment zones, without compromising treatment safety.

[Ultrasonographic features of retinal pigment epithelial adenoma].

Objective: To investigate the ultrasonographic features of retinal pigment epithelium (RPE) adenoma. Methods: It was a retrospective case series study. The clinical clata of 15 patients (15 eyes) with pathologically confirmed RPE adenoma after local resection of intraocular tumor was collected at Beijing Tongren Hospital, Capital Medical University from November 2013 to October 2019. The general conditions of the patients and the location, size, shape, internal echo features of the lesions in the ocular ultrasound sonogram were analyzed, and the blood flow in the lesions was checked by color Doppler flow imaging (CDFI). Results: Of all the patients included in the study, 7 were male and 8 were female. Their age ranged from 25 to 58 years, with a mean age of (45.7±10.2) years. The most common symptom was vision loss or blurred vision (11 cases). Other symptoms included dark shadows or obscuration in front of the eyes (3 cases) and no symptoms (1 case). A history of previous ocular trauma was present in one case, and the rest of the patients had no history of ocular trauma.The location of tumor growth is scattered. The ultrasonographic features were as follows: the average maximum basal diameter was (8.07±2.75) mm and the average height was (4.02±1.81) mm; the ultrasonographic features mostly demonstrated abruptly elevated dome-shaped echo (6 cases); the lesion edge was not smooth, the internal echo was medium or low, and there could be hollow features (2 cases), with no choroidal depression; and the blood flow signal could be seen in the CDFI lesion, which could lead to retinal detachment and vitreous opacification. Conclusion: The ultrasound imaging features of RPE adenomas mostly demonstrate abruptly elevated dome-shaped echo, unsmooth lesion edge, with no choroidal depression, which may provide valuable evidence for clinical diagnosis and differentiation.

[Altered dynamics of brain spontaneous activity in betel quid dependence chewers].

Objective: To investigate the dynamic characteristics of brain spontaneous activity in betel quid dependence (BQD) chewers and its relationship with clinical indexes. Method: This study was conducted in Hainan General Hospital from April to December 2019 and the data of 53 BQD chewers (37 males and 16 females, aged 20 to 58(38±11) years) and 37 healthy controls (HC) (24 males and 13 females, aged 23-57(42±12) years) were collected. All these subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scan. The dynamic characteristics of resting fMRI indexes, including dynamic amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo) and degree centrality (DC) of these subjects were calculated using the sliding time window method, parameters such as age and dynamic local consistency were analyzed and compared between the two groups. Pearson correlation was used to analyze the relationship between dynamic indexes, betel quid dependence score (BQDS) and disease duration in BQD group. Results: BQD chewers showed decreased dynamic ALFF in the left orbital prefrontal cortex (0.138±0.041 vs 0.171±0.070), the right temporal pole superior temporal gyrus (0.277±0.070 vs 0.319±0.086) and the right inferior parietal lobule (0.223±0.052 vs 0.259±0.088) than HC (all P<0.05). For regional homogeneity, BQD chewers showed a decrease dynamic ReHo in the right inferior temporal gyrus (0.055±0.008 vs 0.061±0.009), the orbital prefrontal cortex (0.058±0.005 vs 0.063±0.008), the right inferior frontal gyrus (0.081±0.006 vs 0.087±0.011), the right superior occipital gyrus (0.056±0.007 vs 0.062±0.008), the left precentral gyrus (0.068±0.008 vs 0.074±0.008), and the left superior frontal gyrus (0.058±0.008 vs 0.064±0.009) than HC (all P<0.05). BQD chewers showed an increase dynamic ReHo in the right precuneus (0.095±0.009 vs 0.089±0.008) (P<0.05). There was no significant difference in DC between the two groups (all P>0.05). The relationships between three dynamic ALFF and BQDS (r=-0.104, -0.015, -0.119), seven dynamic ReHo and BQDS (r=-0.099, -0.141, -0.055, -0.078, -0.027, -0.111, -0.090), three dynamic ALFF and disease duration (r=-0.122, -0.095, -0.171), and seven dynamic ReHo and disease duration (r=0.242, -0.252, 0.035, 0.056, 0.047, 0.081, 0.169) were not statistically significant (all P>0.05). Conclusions: BQD chewers showed a decrease dynamic ReHo and/or ALFF in multiple brain regions dominated by prefrontal cortex, and an increase dynamic ReHo in the right precuneus.

H-FABP gene expression and genetic association with meat quality traits in domestic pigeons (Columba livia).

1. H-FABP (heart-type fatty acid-binding protein) is an important fatty acid-binding protein that participates in the metabolism and intracellular transportation of lipids. This study was designed to study the H-FABP gene expression and genetic association with meat quality traits in domestic pigeons.2. The spatio-temporal expression patterns showed that H-FABP was widely expressed in all eleven tissues in birds from hatching to 4 weeks of age, and the expression level in the liver was the highest, and spleen and subcutaneous fat showed relatively high levels at all time points, and increased markedly as squabs became older.3. Nine novel SNPs were found; three of them (g.42 C > T and g.123 C > T in exon 1 and g.3128 C > T in exon 2) were synonymous mutations, and six of them (g.3304 T > C, g.3305 G > A, g.3313A>G, g.3343 C > T, g.3372A>C, g.3410 T > C in exon 3) were located in the 3' untranslated region (UTR). In addition, four haplotypes and six diplotypes were formed and showed weak linkage disequilibrium. Association analysis showed that in the SNP of g.3305 G > A, the AB genotype showed higher (P < 0.05) inosinic acid concentrations in breast muscle than the BB genotype. In the SNP of g.3313A>G, the AA and AB genotypes showed significantly higher (P < 0.01) inosinic acid concentrations than the BB genotype, AA showed the highest intramuscular fat content, and the relative mRNA expression level of the AA genotype was the highest (P < 0.05).4. Association analysis of diplotypes showed no correlation with meat quality traits. Moreover, correlation analysis indicated that the H-FABP mRNA expression level was tightly related to intramuscular fat content (P < 0.01).5. This study suggested that the H-FABP gene may be a candidate gene in marker-assisted selection of pigeons for high-quality meat.

Diagnostic value of ultrasound elastography for differentiation of benign and malignant axillary lymph nodes: a meta-analysis.

AIM: To investigate the diagnostic value of ultrasound elastography (UE) for benign and malignant axillary lymph nodes. MATERIALS AND METHODS: A literature search was conducted from PubMed, Cochrane EMBASE, and Medline. Fourteen studies including 1,186 patients with 1,411 lymph nodes were enrolled. Overall, diagnostic descriptive statistics included pooled sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) with corresponding 95% confidence intervals (95% CIs) were generated by random effect model. Subgroup analyses were performed in (real-time elastography [RTE] versus shear wave elastography [SWE]) and (conventional ultrasound versus combination of traditional ultrasound and elastography). Meta-regression was used to explore potential sources of heterogeneity. RESULTS: The overall pooled sensitivity, specificity, and AUC of UE was 0.79 (95% CI: 0.71-0.86), 0.90 (95% CI: 0.83-0.95), and 0.91 (95% CI: 0.88-0.93), respectively. In the subgroup analysis of the two UE techniques, the pooled sensitivity, specificity, and AUC of SWE was higher than that of RTE (sensitivity: 0.82>0.77; specificity: 0.91>0.89; AUC: 0.94>0.89). The pooled diagnostic value of ultrasound combined with UE were significantly improving compared with traditional ultrasound (sensitivity: 0.87>0.82, specificity: 0.83>0.78, and AUC: 0.91>0.87). No independent heterogeneous factor was found in meta-regression. CONCLUSION: The results indicate that UE was an effective technique for identifying malignant axillary lymph nodes due to its high diagnostic efficiency, which can provide useful information for surgical procedure selection.

[Application of intravenous sedation in 2 582 cases of oral and maxillofacial surgery].

OBJECTIVE: To analyze the clinical data of patients undergoing intravenous sedation in oral and maxillofacial surgery, to understand the epidemiological characteristics, to evaluate the efficacy and safety of intravenous sedation for oral surgery, and to summarize our experience. METHODS: We retrospectively reviewed the clinical data of patients undergoing intravenous sedation between January 2010 and December 2018 in the Department of Oral and Maxillofacial Surgery, Peking University School of Stomatology. The gender, age, source, disease types, the values of perioperative vital signs, the use of sedatives and analgesics, duration of surgery and sedation, effect of sedation during the operation and the postoperative anterograde amnesia were analyzed. RESULTS: A total of 2 582 patients experienced oral surgery by intravenous sedation. The peak age was 3.5 to 10 years and between 21 to 40 years. Supernumerary teeth (38%, 981/2 582) and impacted third molars (30%, 775/2 582) were the major disease types, and other types of disease accounted for 32 percent (826/2 582). The values of heart rate(HR), mean arterial pressure(MAP), respiration rate(RR) and bispectral index(BIS) showed statistically significant differences at the time of before sedation, local anesthesia injection, surgical incision, 10 min after operation and the end of operation. In the study, 69%(1 781/2 582) cases received midazolam alone, 7%(181/2 582) cases received propofol alone, and 24% (620/2 582) cases received midazolam and propofol combined for intravenous sedation. Fentanyl (33%, 852/2 582)was the most common intravenous analgesic we used, followed by flurbiprofen axetil (23%, 594/2 582) and ketorolac tromethamine (6%, 157/2 582). Besides, 35% (907/2 582) patients didn't use any intravenous analgesic during the surgery. The average operation time was (31.2±20.8) min, and the average sedation time was (38.4±19.2) min. During the surgery procedure, most of the patients scored on a scale of 2 to 4 according to the Ramsay sedation score (RSS). The postoperative anterograde amnesia rates of local anesthesia injection, surgical incision and dental drill during surgery were 94% (2 431/2 582), 92% (2 375/2 582) and 75% (1 452/1 936). CONCLUSION: Intravenous sedation on the oral and maxillofacial surgery is effective and safe, can make the patients more comfortable, and should be further promoted and applied.

[Analysis of pathogen spectrum and antimicrobial resistance of pathogens associated with hospital-acquired infections collected from 11 teaching hospitals in 2018].

Objective: To investigate the spectrum and antimicrobial resistance of major pathogens causing nosocomial infections in China, 2018. Methods: Non-duplicated nosocomial cases as well as pathogens causing bloodstream infections (BSI), hospital-acquired pneumonia (HAP) and intra-abdominal infections (IAI) from 11 teaching hospitals across China were collected. The minimum inhibitory concentrations (MICs) of clinically significant strains were determined by agar dilution method or broth microdilution method. The Clinical and Laboratory Standards Institute (CLSI) M100-S29 criteria were used for interpretation, and the WHONET-5.6 software was used in data analysis. Results: A total of 1 590 cases were collected, including 831 cases from BSI, 450 cases from HAP and 309 cases from IAI. The most prevalent pathogens causing BSI were Escherichia coli (29.2%, 243/831), Klebsiella pneumoniae (16.2%, 135/831) and Staphylococcus aureus (10.1%, 84/831); the most prevalent pathogens causing IAI were E. coli (26.2%, 81/309), Enterococcus faecium (15.5%, 48/309) and K. pneumoniae (13.3%, 41/309); while Acinetobacter baumanii (24.7%, 111/450), Pseudomonas aeruginosa (20.7%, 93/450) and K. pneumoniae (16.2%, 73/450) were dominated in HAP. All S. aureus were susceptible to tigecycline, linezolid, daptomycin and glycopeptides; 77.8% (105/135) of S. aureus strains were susceptible to ceftaroline. Methicillin-resistant S. aureus (MRSA) accounted for 29.6% (40/135) of all the S. aureus, and was lower than the accounted rate of methicillin-resistant coagulase-negative Staphylococcus (MRCNS) (83.7%, 41/49). One E. faecium strain (1.1%, 1/95) resistant to vacomycin and teicoplanin and one E. faecalis strain (2.3%, 1/43) resistant to linezolid was found. The prevalence of extended-spectrum ß-lactamase (ESBL) was 56.1% (193/344) in E. coli and 22.1% (55/249) in K. pneumonia; the rate of carbapenem resistant E. coli and K. pneumonia was 4.1% (14/344) and 22.9% (57/249), respectively; the percentage of ceftazidime/avibactam resistant E. coli and K. pneumonia was 2.3% (8/344) and 2.0% (5/249), respectively; the percentage of colistin resistant E. coli and K. pneumonia was 1.5% (5/344) and 7.6% (19/249), respectively; no E. coli and K. pneumonia strains were found resistant to tigecycline. The rate of carbapenem resistant A. baumanii and P. aeruginosa were 78.9% (146/185) and 36.7% (66/180), respectively. A. baumanii showed low susceptibility to the antimicrobial agents except colistin (99.5%, 184/185) and tigecycline (91.4%, 169/185). Colistin, amikacin and ceftazidime/avibactam demonstrated high antibacterial activity against P. aeruginosa with susceptility rate of 100% (180/180), 93.3% (168/180) and 85.6% (154/180), respectively. Conclusions: Nosocomial Gram-negative pathogens show high susceptibilities to tigecycline, colistin and ceftazidime/avibactam in vitro. Antimicrobial resistance in A. baumannii is a serious problem. The prevalence of carbapenem-resistant Enterobacteriaceae has increased, which should be monitored continuously in China.

[Clinical histopathologic characteristics of lacrimal glands in lacrimal gland prolapse with blepharochalasis].

Objective: To analyze the clinical histopathologic characteristics of lacrimal glands and possible mechanisms of lacrimal gland prolapse in blepharochalasis (BC). Methods: A case-controlled study of 23 consecutive patients with prolapse of lacrimal glands in BC was performed. All samples were obtained during surgery from the Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University between January 2009 and December 2016. The lacrimal tissue included prolapsed lacrimal glands (30 samples) and controls from the donors in the eye bank of Beijing Tongren Hospital, Capital Medical University (8 samples). Hematoxylin-eosin staining, special staining, immunohistochemistry and colloidal gold-labeled pre-embedded indirect immunogold electron microscopy (Gold-IIEM) were performed to analyze the histopathologic characteristics of the samples. The nonparametric Wilcoxon signed-ranks test was carried out for statistical analysis. Results: Among the 23 patients with lacrimal gland prolapse in BC, there were 3 males and 20 females. The mean age of morbidity was 11 years old (7-16 years). In the 8 normal control cases, 3 males and 5 females were included. The mean age was 15 years (10-20 years). In the 30 prolapsed lacrimal gland samples, hematoxylin-eosin staining showed enlargement of glandular lumina accompanied by inflammatory infiltrates of interstitial tissue in 2 samples. Marked loosening of collagen fibers of the obtainable lacrimal fascia was observed. The results on immunohistochemical staining demonstrated an increased level of immunocytes in the 30 prolapsed lacrimal gland samples, including IgA (+++, ++, +, -; 12, 11, 4, 3 vs. 0, 0, 1, 7; Z=-3.892), CD3(+)T cells (+++, ++, +, -; 2, 19, 7, 2 vs. 0, 0, 1, 7; Z=-4.168), matrix metalloproteinase (MMP)-3 (+++, ++, +, -; 0, 0, 11, 19 vs. 0, 0, 0, 8; Z=-2.005) and MMP-9 (+++, ++, +, -; 14, 14, 0, 2 vs. 0, 0, 0, 8; Z=-4.552) (all P<0.05). IgG, IgM, CD20 and C1-inhibitor were either absent or expressed at background level in the 30 prolapsed lacrimal gland samples (all P>0.05). Gold-IIEM showed zymogon granules in lacrimal glands were out of shape. MMP-3 and MMP-9 colloidal gold particles existed on the zymogon granules, and MMP-3 colloidal gold particles also existed on the surface of lacrimal gland epithelial cells. Conclusions: The histopathological changes in the lacrimal glands of lacrimal gland prolapse with BC include inflammatory infiltration, elastic fiber degeneration, marked loosening of the supporting fascia tissue, and an increased level of immunocytes, including IgA, CD3(+)T cells, MMP-3 and MMP-9. The results suggest that lacrimal gland prolapse with BC may result in the immuno-pathogenetic mechanisms with the involvement of cell-mediated immune responses. (Chin J Ophthalmol, 2020, 56: 205-210).

[Ocular manifestations and surgical treatment of the linear nevus sebaceous syndrome].

Objective: To report the clinical and pathological features and surgical treatment of the linear nevus sebaceous syndrome. Methods: It was a retrospective case series study. The clinical records of 11 patients (14 eyes) who were diagnosed as linear nevus sebaceous syndrome between April 2009 and February 2018 at Beijing Tongren Hospital were analyzed. Data collected included sex, age, clinical manifestations, disease site, pathological features, surgical treatment and therapeutic effects. Results: There were six males and five females, aged 6 months to 7 years (mean, 2.8 years). The nevus sebaceous was located at the head (9 patients), face (5 patients) and neck (3 patients). The most common ocular manifestations were blepharocoloboma (13 eyes) and external ocular mass (9 eyes). Surgical treatment was performed in 9 patients (11 eyes), including lid reconstruction in all these eyes, corneal and conjunctival mass resection in four patients (4 eyes), eyelid tumor resection in 5 patients (5 eyes), and symblepharon separation and conjunctival sac reconstruction in 3 patients (5 eyes). Pathological examinations of the external ocular, corneal and conjunctival masses (6 eyes) confirmed the diagnosis of complex choristoma. All operated patients had improved appearance. Conclusions: Linear nevus sebaceous syndrome has characteristic cutaneous lesions and ocular manifestations. Histopathologically, all epibulbar lesions prove to be complex choristomas. The appearance of patients with linear nevus sebaceous syndrome can be significantly improved by oculoplastic surgery. (Chin J Ophthalmol, 2020, 56: 846-852).

[Application of digital mandibular movement record and masticatory muscle electromyography in the evaluation of stomatognathic function in patients with mandibular tumor].

OBJECTIVE: To study the clinical characteristics of mandibular movement and masticatory muscle function in preoperative and postoperative patients with unilateral mandibular tumors in the region of mandibular body and ramus by combining digital mandibular movement records with electromyography, and to preliminarily explore the relationship and mechanism between movement and masticatory muscle function. METHODS: Six preoperative patients with tumor in unilateral body and ramus of mandible were included, and three postoperative patients with unilateral segmental resection and reconstruction of mandibular bone were included. The mandibular movement recording system and surface electromyography system were used to collect the movement trajectory of the patients' mandibular marginal movement and chewing movement, and the surface electromyography of bilateral masseter and temporalis was recorded concurrently. The surface electromyography of bilateral masseter and temporalis was collected when the patients were at relaxation and at maximal voluntary clenching (MVC). The motion trajectory was observed on the digital virtual model, and the motion amplitude and direction of mandibular marginal movements were analyzed. The characteristics of masticatory electromyogram (EMG) activity in affected and unaffected sides at relaxation, MVC and bilateral mastication were analyzed, and the asymmetry indexes and activity indexes were calculated. RESULTS: The preoperative mean maximum opening of the patients was (35.20±6.87) mm. Three patients had mild mouth opening limitation, and all the patients' mouth opening trajectory was skewed to the affected side. During lateral movements, the mean range of motion of the affected side [(10.34±1.27) mm] and that of the healthy side [(6.94±2.41) mm] were significantly different. The maximum opening of the postoperative patients was (30.65±17.32) mm, and the mandibular marginal movement characteristics were consistent with those of the patients before surgery. During MVC in the preoperative patients, the median EMG activities of the masseter muscle [44.20 (5.70, 197.90) µV] and the temporalis muscle [42.15 (22.90, 155.00) µV] on the affected side were slightly lower than those of the masseter [45.60 (7.50, 235.40) µV] and the temporalis muscle [63.30 (44.10, 126.70) µV] on the healthy side. In the postoperative patients, individualized changes occurred. Some patients suffered from weakened electromyographic activity on the affected side, while some other ones showed hyperelectromyographic activity on the affected side. CONCLUSION: Both benign and malignant tumors as well as their surgery can cause abnormal mandibular movements and change of electromyographic activity of bilateral masseter and temporalis muscles.

Phase 2a, randomized, double-blind, placebo-controlled, multicentre, parallel-group study of an H4 R-antagonist (JNJ-39758979) in adults with uncontrolled asthma.

BACKGROUND: The effects of H4 R antagonists in preclinical asthma models support the study of antagonists of the H4 R in the treatment of asthma in humans. JNJ-39758979 is a potent and highly selective oral H4 R antagonist. OBJECTIVE: We sought to evaluate the safety and efficacy of the H4 R-antagonist JNJ-39758979 in adult patients with uncontrolled asthma. METHODS: One hundred and fifteen eligible patients were randomly assigned to JNJ-39758979 300 mg or placebo once daily for 12 weeks in this phase 2a, double-blind, multicenter, placebo-controlled study. Primary efficacy was assessed via week-12 change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1 ). Secondary efficacy assessments included patient-reported outcome (PRO) asthma assessments (Asthma Daily Diary data [AM and PM peak expiratory flow rate, number of puffs of albuterol/salbutamol, the presence of nocturnal awakenings and asthma symptom score]). RESULTS: The study did not meet the primary end-point. However, nominally significant improvements in pre-bronchodilator FEV1 were observed with JNJ-39758979 versus placebo at week 12 in pre-specified subgroups with elevated exhaled nitric oxide, sputum eosinophils or blood eosinophils at baseline. Nominally significant improvements across PRO assessments were consistently observed in the overall population, as well as in eosinophilic subgroups. Safety, such as adverse event rates, was comparable between JNJ-39758979 and placebo. No serious adverse events were reported. No clinically relevant changes in laboratory values were observed. CONCLUSIONS AND CLINICAL RELEVANCE: The findings suggest potential benefit of H4 R antagonists on lung function and asthma control in eosinophilic asthma patients and warrant further evaluation of this mechanism in asthma with eosinophilic inflammation. NCT00946569.

The added value of contrast-enhanced ultrasound to conventional ultrasound in differentiating benign and malignant solid breast lesions: a systematic review and meta-analysis.

AIM: To investigate the added value of contrast-enhanced ultrasound (CEUS) to the conventional ultrasound (US) in the diagnosis of breast lesions. MATERIALS AND METHODS: PubMed, EMBASE, and Web of Science were searched for relevant studies published between 24 May 2005, and 29 October 2017. Studies incorporating CEUS into the conventional US were included. The reference standard was set by means of histopathological findings. The quality assessment of diagnostic studies (QUADAS) instrument was used to assess the quality of the included studies. Meta-Disc version 1.4. was used to calculate the sensitivity, specificity, summary receiver-operating characteristic (sROC) curves, and area under the curve (AUC). Meta-regression with Stata 12.0 was used to compare the diagnostic accuracy of the two techniques. RESULTS: Five studies, comprising 992 patients, were eligible for this meta-analysis. For conventional US, the pooled sensitivity and specificity for were 0.87 (95% confidence interval [CI]: 0.84-0.91) and 0.80 (95% CI: 0.76-0.84), respectively, the AUC was 0.9049. For CEUS-rerated US, the pooled sensitivity and specificity were 0.93 (95% CI: 0.90-0.95) and 0.87 (95% CI: 0.84-0.90). The AUC was 0.9482. Meta-regression showed the sensitivity of CEUS-rerated US did not differ from conventional US (p=0.29), while specificity showed significant difference (p<0.01). There was evidence of between-study heterogeneity regarding sensitivity and specificity for both assessments. CONCLUSIONS: Adding CEUS to conventional US could improve the diagnostic performance in differentiating benign from malignant solid breast lesions, whilst retaining high sensitivity, especially in Breast Imaging-Reporting and Data System (BI-RADS) 3-5 lesions. A uniform standard to distinguish benign from malignant lesions might be needed for further clinical application.

Effects of N-carbamylglutamate and L-arginine on gonadotrophin-releasing hormone (GnRH) gene expression and secretion in GT1-7 cells.

Recent studies have shown that N-carbamylglutamate (NCG) and arginine (ARG) supplementation improves reproductive performance in livestock. The objectives of the present study were to evaluate the effects of NCG and ARG on GT1-7 cell gonadotrophin-releasing hormone (GnRH) secretion, gene expression and cell proliferation. GT1-7 cells were treated in vitro with different concentrations of NCG (0-1.0mM) or ARG (0-4.0mM) in serum-free medium for 12 or 24h. For GnRH secretion and cell proliferation, GT1-7 cells were more sensitive to NCG than ARG. NCG treatment after 12h increased cell numbers and inhibited GnRH secretion in a dose-dependent manner (P<0.05), although there was no significant effect of NCG on these parameters after 24h culture. ARG treatment decreased GnRH secretion after 24h (P<0.05), whereas it had no effect after 12h. GT1-7 cells express GnRH, Kiss-1 metastasis-suppressor (Kiss1), G-protein coupled receptor 54 (GPR54), neuronal nitric oxide synthase (nNOS) and estrogen receptor α (ERα) genes. High concentrations of NCG (1.0mM) and ARG (4.0mM) inhibited (P<0.05) GnRH and nNOS mRNA abundance in GT1-7 cells. ARG treatment decreased Kiss1 and increased ERα mRNA abundance. Thus, high concentrations of NCG (1.0mM) and ARG (4.0mM) may act both directly and indirectly to regulate GnRH neuron function by downregulating genes related to GnRH synthesis and secretion to slow GnRH production while stimulating GT1-7 cell proliferation.

N-octanoylated ghrelin peptide inhibits bovine oocyte meiotic resumption.

BACKGROUND: Studies have shown that ghrelin plays an important role in the mammalian reproductive system, including the central, gonadal levels, and also during in vitro maturation of oocytes; however, the functions of ghrelin in bovine oocyte meiosis require further investigation. OBJECTIVE: We aimed to evaluate the effects of an n-octanoylated ghrelin peptide on oocyte meiotic resumption and the developmental competence of mature oocytes in vitro. EXPERIMENTAL: design: The expression of GHRL (encoding ghrelin) mRNA and its receptor (the growth hormone secretagogue receptor, GHSR) in the cumulus-oocyte complex (COCs), denuded oocytes (DOs), and cumulus cells (CCs) was assessed using quantitative real-time reverse transcription PCR (qRT-PCR), and the effects of the n-octanoylated ghrelin peptide on meiotic resumption were studied at four different doses (0, 10, 50, and 100 ng/mL) in a 6 h culture system. RESULTS: qRT-PCR analysis showed that GHRL and GHSR mRNAs were expressed in all tested samples; however, GHRL was predominantly expressed in DOs, and GHSR was predominantly expressed in CCs. Germinal vesicle breakdown was inhibited significantly by 50 ng/mL ghrelin compared with that in the negative control (P < 0.05). Further studies showed that n-octanoylated ghrelin increased the levels of cAMP and cGMP in the CCs and DOs, which inhibited the meiotic resumption of bovine oocytes. And the inhibitory role in the developmental competence of mature oocytes were also included, ghrelin could significantly improve the cleavage rate (P < 0.05) and blastocyst rate (P < 0.05). CONCLUSION: N-octanoylated ghrelin maintained bovine oocytes meiotic arrest and further improved their developmental competence; therefore, n-octanoylated ghrelin could be considered as a potential pharmaceutical inhibitor of meiosis for the in vitro maturation of bovine oocytes.

[Mammary myofibroblastoma: a clinicopathologic analysis of nine cases].

Objective: To study the clinicopathologic characteristics and differential diagnosis of mammary myofibroblastoma. Methods: Nine cases of mammary myofibroblastoma diagnosed between 2006 and 2017 were collected from the Department of Pathology, Fudan University Shanghai Cancer Center. Clinical and histopathologic features of these nine cases were examined, immunohistochemical staining was performed, FISH analysis for the detection of FOXO1 gene was performed in one case, and follow-up data were also collected. Results: There were seven female and two male patients, with a mean age of 54 years, median age of 50 years (ranging from 40 to 83 years). Four lesions each were located in the left and right breast, and one was in the left subaxillary accessory breast tissue. Clinically, 8 patients presented with a breast mass, 3 of which accompanied with pain. All of the tumors were well-demarcated grossly with a mean diameter of 2.5 cm. Microscopically, there were no entrapped ductal or lobular structures within the tumor. Seven tumors were classic type, which were composed of bland-looking spindle neoplastic cells without mitoses, arranging in intersecting fascicles, and interrupted by thick hyalinized collagen bundles. One case was of epithelioid variant, demonstrating epithelioid neoplastic cells diffusely arranged or in cluster. The other one case was mixed spindle and epithelioid-cell type. Atypical tumor cells were observed in 3 cases. Immunohistochemically, tumor cells were diffusely positive for desmin (9/9) and CD34 (6/9), as well as ER (7/7), PR (6/6) and bcl-2 (3/3). SMA (4/7) and Calponin (1/2) were focally or partially positive in some cases. H-caldesmon (1/2) was weakly positive and epithelial markers were negative. Ki-67 proliferation index was low (<10%). There was no monoallelic loss of FOXO1/13q14 loci in the detected case according to FISH analysis. Follow-up data were available for all patients, and follow-up period ranged from 12 to 78 months. All patients remained well without recurrence. Conclusions: Mammary myofibroblastoma is a rare benign mesenchymal tumor. In some circumstances, it may exhibit confusing morphologies, including some variants. The epithelioid variant of mammary myofibroblastoma might mimic invasive lobular carcinoma, leading to the diagnostic dilemmas and even misdiagnosis, especially in core needle biopsy specimen or frozen sections. Familiarity with the characteristics of this tumor is of great importance for accurate diagnosis and proper treatment.

[Angiofibroma of soft tissue: a clinicopathologic analysis of 24 cases].

Objective: To investigate the clinicopathologic and genetic features, pathologic diagnosis and differential diagnosis of angiofibroma of soft tissue(AFST). Methods: The clinicopathologic characteristics of 24 cases diagnosed at Fudan University Shanghai Cancer Center from 2011 to 2017 were analyzed; immunohistochemical staining and interphase fluorescence in situ hybridization (FISH) were performed, and the literatures were also reviewed. Results: There were 15 male and 9 female (male∶female=1.7∶1.0) patients with age of onset ranging from 8 to 68 years (mean, 45 years). Fourteen cases occurred in extremities, including upper limbs (n=3) and lower limbs (n=11); seven cases were in the trunk, and 1 case each was in the temporal region, retroperitoneum and liver, respectively. Clinically, the tumors usually presented as a slowly growing painless mass. Tumor sizes ranged from 0.8 to 14 cm (mean 4.6 cm). Microscopically, most lesions were well-circumscribed, with fibrous capsules. Few cases infiltrated the surrounding fibrofatty tissue focally. The tumors were mainly composed of sparse short spindle cells and numerous small, branching, thin-walled blood vessels distributed in amyxoid, fibromyxoid or collagenous matrix, often accompanied by medium-sized, round or irregular and ecstatic vessels at the tumor periphery.By immunohistochemistry, all tested cases expressed vimentin (5/5), and showed variable positivity for EMA (2/4), ER (1/2), PR (2/3), α-SMA (1/18)and desmin (1/10). Ki-67 proliferation index were all less than 5%. CD34, CD31 and ERG staining clearly outlined the contours of blood vessels in the stroma. Four cases were tested for NCOA2 gene rearrangement by FISH, of which three were positive. Follow-up data was available in 17 patients (range, 3 to 69 months; mean, 30 months) were all free of disease. Conclusions: Soft tissue angiofibroma is a benign fibroblastic neoplasm characterized by a prominent and complex vasculature set in a myxoid-to-collagenous stroma, and cytogenetically a distinctive NCOA2 gene rearrangement. Caution should be exercised for the possibility of potentially misinterpretation of AFST as vascular tumors and other myxoid soft tissue tumors.

[Analysis of high-risk histopathologic features of 482 primarily enucleated retinoblastomas].

Objective: To evaluate the high-risk histopathologic features of retinoblastoma eyes enucleated as primary treatment. Methods: Retrospective case series study. An analysis was carried out on the high-risk histopathologic features of 482 primarily enucleated retinoblastoma eyes in Beijing Tongren Eye Center during December 2011 and December 2016. The high-risk histopathologic features included post lamina cribrosa invasion, massive choroidal invasion, anterior segment invasion and extraocular invasion. According to the neovascularization of iris (NVI) in the tissue specimen, the patients were divided into the NVI positive group and negative group. The rates of high-risk histopathologic features in the NVI positive group and negative group were analyzed using the chi-square test. Results: Among 482 children with retinoblastoma, 280 (58.1%) were males and 202 (41.9%) were females. The median age at enucleation surgery was 24 months (range, 1-84 months). Of the 482 primarily enucleated eyes, 184 (38.2%) were classified as high-risk histopathologic features, including 148 (30.7%) with post lamina cribrosa invasion, 15 (3.1%) with optic nerve transection invasion, 66 (13.7%) with massive choroidal invasion, 35 (7.3%) with anterior segment invasion, and 5 (1.0%) with extraocular invasion. NVI was detected in 257 (53.3%) cases and there was a significant relation between high-risk histopathologic features and NVI. The rate of high-risk histopathologic features was significantly higher in the NVI positive group (123 cases, 47.9%) than the NVI negative group (61 cases, 27.1%) (χ(2)=21.883, P=0.001). The rate of post lamina cribrosa invasion was significantly higher in the NVI positive group (110 cases, 42.8%) than the NVI negative group (38 cases, 16.9%) (χ(2)=37.860, P=0.001). Conclusions: In this large sample of patients, about 1/3 of retinoblastoma eyes has high-risk histopathologic features. The NVI positive retinoblastoma is more likely to have high-risk histopathologic features or post lamina cribrosa invasion than the NVI negative retinoblastoma. (Chin J Ophthalmol, 2018, 54: 782-786).

Femtosecond Probing of Plasma Wakefields and Observation of the Plasma Wake Reversal Using a Relativistic Electron Bunch.

We show that a high-energy electron bunch can be used to capture the instantaneous longitudinal and transverse field structures of the highly transient, microscopic, laser-excited relativistic wake with femtosecond resolution. The spatiotemporal evolution of wakefields in a plasma density up ramp is measured and the reversal of the plasma wake, where the wake wavelength at a particular point in space increases until the wake disappears completely only to reappear at a later time but propagating in the opposite direction, is observed for the first time by using this new technique.