[Comparison of efficacy between short-term personalized vestibular rehabilitation supervised by special personnel and fixed vestibular rehabilitation on recurrent peripheral vertigo].

Objective: To explore the efficacy of short-term personalized vestibular rehabilitation supervised by special personnel (ST-PVR) versus fixed vestibular rehabilitation (FVR) on decompensated recurrent peripheral vertigo. Methods: A randomized controlled trial was carried out. Patients diagnosed with decompensated recurrent vertigo in the clinic of Eye & ENT Hospital, Fudan University from January to December 2018 were randomly allocated into FVR and ST-PVR groups via computer-generated randomization. The FVR group received fixed scheme involving gaze stabilization exercises, habituation exercises, balance and gait training, while the ST-PVR group received individualized training programs based on symptoms and vestibular function examination results, with adjustments made according to the progress of recovery. Patient symptoms and vestibular function improvement were assessed using the dizziness handicap inventory (DHI), activities-specific balance confidence (ABC), self-rating anxiety scale (SAS), caloric test, and sensory organization test (SOT) at 2, 4, and 8 weeks of treatment. Results: A total of 44 patients were included, including 16 males and 28 females, with an average age of (50.6±13.5) years. There were 21 cases in the FVR group and 23 cases in the ST-PVR group. In the ST-PVR group, DHI score (49.5±26.8 vs 61.3±21.4, P=0.046) and SAS score (39.1±7.8 vs 44.3±6.6, P=0.021) significantly improved after 2 weeks of treatment, while significant improvement occurred only after 8 weeks of treatment in the FVR group (DHI score: 28.1±15.9 vs 53.1±18.5, P=0.001; SAS score: 35.3±6.7 vs 43.1±8.4, P=0.010). There was no significant change of ABC score in the FVR group after 8 weeks of treatment (86.5±12.9 vs 83.4±18.1, P=0.373), while a significant improvement was observed in the ST-PVR group after 4 weeks of treatment (83.6±15.2 vs 78.4±15.1, P=0.015). The caloric test results showed that after 8 weeks of treatment, the proportion of patients with unilateral weakness<25% increased in both groups [FVR group: 57.1% (12/21) vs 9.5% (2/21), P=0.001; ST-PVR group: 52.2% (12/23) vs 17.4% (4/23), P=0.014]. In the ST-PVR group, the proportion of patients with dominant preference≤25% significantly increased [91.3% (21/23) vs 60.9% (14/23), P=0.016], while there was no significant change in the FVR group [61.9 (13/21) vs 57.1% (12/21), P=0.500]. The proportion of patients with SOT score≥70 in the ST-PVR group increased significantly after 2 weeks of treatment [69.6% (16/23) vs 30.4% (7/23), P=0.009], while the FVR group showed a significant increase only after 8 weeks of treatment [81.0% (17/21) vs 42.9% (9/21), P=0.012]. Conclusion: Both FVR and ST-PVR effectively promote vestibular compensation by improving objective vestibular functions and relieving subjective symptoms and anxiety of the patients with decompensation recurrent vertigo, while ST-PVR might shorten the recovery time and increase balance confidence.

[Randomized controlled study on the application effect of a new type of intravenous radiofrequency closed therapy system made in China and an imported system].

Objective: To compare the application effect of domestic and imported intravenous radiofrequency closure system in the treatment of primary varicose veins of lower extremities. Methods: This single-center prospective, non-inferiority randomized controlled trial was performed in the Department of Vascular Surgery, the Fourth Affiliated Hospital, Zhejiang University School of Medicine from January 2021 to January 2022. Patients with primary varicose veins of lower extremities who met the ataxation criteria were randomly assigned to the experimental group(domestic novel venous radiofrequency closure system) or the control group(imported venous radiofrequency closure system) in a ratio of 1∶1. The two groups of subjects were compared in terms of target vein closure rate, technical success rate, system operation performance, incidence of adverse events and incidence of serious adverse events(SAE) within 6 months after surgery. Quantitative data were compared by Mann-Whitney U test, and categorical data were compared by χ2 test and non-inferiority test. Results: A total of 80 subjects were included in the trial (41 in the experimental group and 39 in the control group), including 27 males and 53 females, aged (M(IQR)) 55(23) years (range:40 to 78 years). There were 48 cases of left lower limb and 32 cases of right lower limb. The technical success rate and system control performance between the groups were 100%.The incidence of adverse events (58.5% (24/41) vs. 61.5% (24/39), χ2=0.075, P=0.784), and the incidence of SAE (7.3% (3/41) vs. 5.1% (2/39), χ2=0.163, P=0.686) within 6 months after surgery in experimental group and control group had no statistical significance. There was one device-related adverse event in each of the two groups. In the experimental group, one patient developed endovenous heat-induced thrombosis after surgery and recovered after taking rivaroxaban tablets. One patient in the control group had pain in the upper right thigh for more than 1 day after operation, which was cured after using analgesic cream. No device-related SAE occurred. The venous closure rate of the experimental group was 100% (38/38) at 6 months after surgery, and that of the control group was 97.4% (37/38). The difference between the two groups was 2.63% (95%CI:-3.19 to 8.45, Z=4.865, P<0.01), and the 95%CI lower limit of the difference in target venous closure rate between two groups was greater than the non-inferiority threshold of -10.00%. Conclusion: The early application effect of the new domestic intravenous radiofrequency closure system in patients with primary varicose veins of lower extremities is in line with expectations, it is not inferior to the imported system.

Endometrioid adenocarcinoma: combined multiparametric MRI and tumour marker HE4 to evaluate tumour grade and lymphovascular space invasion.

AIM: To assess the value of semi-quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and quantitative diffusion-weighted imaging parameters combined with human epididymis protein 4 (HE4) in predicting the pathological grade and lymphovascular space invasion (LVSI) of endometrioid adenocarcinoma (EAC). MATERIALS AND METHODS: Between October 2018 and December 2021, 60 women (mean age, 55 [range, 32-77] years) with EAC underwent preoperative pelvic MRI and HE4 level measurements. The positive enhancement integral (PEI), time to peak, maximum slope of increase (MSI), and maximum slope of decrease were measured by manually drawing a region of interest on the neoplastic tissue. The receiver operating characteristic curve was used to calculate the diagnostic efficiency of the single parameter and combined factors. RESULTS: Lower apparent diffusion coefficients (ADCs) were observed in high-grade tumours (G3) than in low-grade tumours (G1/G2). PEI, MSI, and HE4 levels were higher in the high-grade tumours than in the low-grade tumours (p<0.05). The area under the curve (AUC) for G3 diagnosis using multiparametric MRI combined with HE4 was 0.929. ADC values were significantly lower in the EAC with LVSI than in those without LVSI. Tumours with LVSI showed higher PEI and HE4 levels than those without LVSI (p<0.05). The AUC for LVSI-positive diagnosis using multiparametric MRI combined with HE4 was 0.814. CONCLUSION: Semi-quantitative DCE-MRI, ADC values, and serum HE4 levels can be used to predict tumour grade and LVSI, and the prediction efficiency of multiparametric MRI combined with serum HE4 is better than that of any single factor.

Long-term safety of risankizumab from 17 clinical trials in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Risankizumab has demonstrated efficacy and safety in patients with moderate-to-severe plaque psoriasis in randomized clinical trials. OBJECTIVES: To evaluate safety data from risankizumab psoriasis phase I-III clinical trials. METHODS: Short-term safety (through week 16) was analysed using integrated data from five phase II and III clinical trials. Long-term safety was evaluated using integrated data from 17 phase I-III completed and ongoing trials. RESULTS: Short-term safety analyses included 1306 patients receiving risankizumab 150 mg and 300 patients receiving placebo [402·2 and 92·0 patient-years (PY) of exposure, respectively]. Long-term analyses included 3072 risankizumab-treated patients (exposure: 7927 PY). The median (excluding four outliers) treatment duration was 2·9 years (range 2 days to 5·9 years). Exposure-adjusted adverse event rates did not increase with long-term treatment (318 vs. 171 events per 100 PY for short- and long-term analyses). With long-term risankizumab treatment, rates of serious adverse events were 7·8 per 100 PY, serious infections 1·2 per 100 PY, nonmelanoma skin cancer (NMSC) 0·7 per 100 PY, malignant tumours excluding NMSC 0·5 per 100 PY, and adjudicated major adverse cardiovascular events 0·3 per 100 PY, with no important identified risks. Limitations include that the study inclusion and exclusion criteria varied and that three studies enrolled ≤ 50 patients. CONCLUSIONS: Risankizumab demonstrated a favourable safety profile over short- and long-term treatment in patients with moderate-to-severe psoriasis.

Psoriasis and metabolic syndrome: implications for the management and treatment of psoriasis.

Psoriasis is a chronic systemic inflammatory disorder associated with several comorbidities in addition to the characteristic skin lesions. Metabolic syndrome (MetS) is the most frequent comorbidity in psoriasis and a risk factor for cardiovascular disease, a major cause of death among patients with psoriasis. Although the exact causal relationship between these two disorders is not fully established, the underlying pathophysiology linking psoriasis and MetS seems to involve overlapping genetic predispositions and inflammatory pathways. Dysregulation of the IL-23/Th-17 immune signalling pathway is central to both pathologies and may be key to promoting susceptibility to metabolic and cardiovascular diseases in individuals with and without psoriasis. Thus, biological treatments for psoriasis that interrupt these signals could both reduce the psoriatic inflammatory burden and also lessen the risk of developing atherosclerosis and cardiometabolic diseases. In support of this hypothesis, improvement of skin lesions was associated with improvement in vascular inflammation in recent imaging studies, demonstrating that the beneficial effect of biological agents goes beyond the skin and could help to prevent cardiovascular disease. This review will summarize current knowledge on underlying inflammatory mechanisms shared between psoriasis and MetS and discuss the most recent clinical evidence for the potential for psoriasis treatment to reduce cardiovascular risk.

Anti-drug antibodies of IL-23 inhibitors for psoriasis: a systematic review.

Anti-drug antibodies (ADAs) can form with certain biological medications, but their clinical significance is not fully understood. ADA formation in psoriasis patients treated with IL-23 inhibitors was evaluated, looking at the incidence of ADAs, impact on clinical outcomes and association with adverse events. A systematic search of PubMed, Cochrane and Embase databases yielded 318 articles, which were manually reviewed. A total of 19 articles met the eligibility criteria. The incidence of ADAs with the IL-23 inhibitors was as follows: 4.1-14.7% with guselkumab, 141-31% with risankizumab and 6.51-18% with tildrakizumab. The incidence of neutralizing antibodies ranged from 01-0.6% with guselkumab, 21-16% with risankizumab and 2.5 to 3.2% with tildrakizumab. There was no evidence of reduced efficacy of psoriasis treatment with ADA presence alone. However, some studies found a reduction in clinical response with high ADA titres or with the presence of neutralizing antibodies. A few studies reported that patients with ADAs to guselkumab and risankizumab had a higher incidence of injection site reactions (ISRs). There do not appear to be other adverse events associated with ADAs with IL-23 inhibitors. Testing for presence of ADAs alone in this patient group does not appear to be predictive of treatment response. Clinically, it may be more productive to test for neutralizing antibodies or ADA titre values, although further investigation is required to show a definitive correlation.

[Expression and regulatory role of ultraconserved long non-coding RNA uc.77 in lung cancer].

Objective: To investigate the effect and molecular mechanism of ultra-conservative long non-coding RNA uc.77 in lung cancer. Methods: Lung cancer tissues and adjacent normal tissues were obtained from 61 patients with lung cancer who were diagnosed with lung cancer and underwent surgery from 2014 to 2016 in the General Hospital of the Southern Theater Command of the People's Liberation Army. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the uc.77 relative expressions in normal human bronchial epithelial cells 16HBE, lung cancer cell lines, and 61 pair lung cancer tissues. Uc.77 siRNA was transfected into lung cancer cells to interfere with the expression of uc.77, qRT-PCR was used to verify the interference effect, CCK8 method and clone formation experiment were used to detect cell proliferation ability, flow cytometry was used to detect apoptosis and cell cycle changes. H1299 cells transfected with uc.77 siRNA were injected into the subcutaneous right side of BALB/c nude mice to construct a tumor-bearing model for exploring the role of uc.77 on tumor growth. Western blot and qRT-PCR methods were used to detect the protein and mRNA expressions of p21. Results: The relative expression levels of uc.77 in lung cancer cell lines 95D, H1299, A549, H460, H446 and 16HBE-T were significantly higher than that of 16HBE cells (P<0.05). The uc.77 RNA expression levels of lung cancer tissues was significantly higher than that of the adjacent normal tissues (P<0.001). In addition, increased lncRNA uc.77 expression was significantly associated with big tumor size, lymph node metastasis and advanced TNM stage (P<0.05). After transfection with uc.77 siRNA, the expressions of uc.77 in H1299, 95-D and 16HBE-T cells were reduced (P<0.05), and the cell proliferation capacities were reduced at 48 hours and 72 hours (P<0.05). After transfection with uc.77 siRNA-1, the G(0)/G(1) phase cell ratio of H1299 siRNA-1 group [(71.86±3.46)%] was higher than those of H1299-control group [(47.62±5.48)%] and H1299 siRNA-NC group [(61.38±5.62)%, P<0.05], S phase cell ratio of H1299 siRNA-1 group [(14.99±3.61)%] was lower than those of H1299-control group [(34.95±7.05)%] and H1299 siRNA-NC group [(23.75±5.87)%, P<0.05], the apoptosis rate of H1299 siRNA-1 group [(4.90±1.80)%] was higher than those of H1299-control group [(3.30±0.80)%] and H1299 siRNA-NC group [(2.80±1.20)%, P<0.05], the colony formation rate of H1299 siRNA-1 group [(19.20±2.00)%] was lower than those of H1299 control group [(32.60±2.00)%] and H1299 siRNA-NC group [(34.40±1.00)%, P<0.05]. The results of the nude mice tumor formation experiment showed that the tumor volume of the H1299 siRNA-1 group was significantly lower than those of the H1299-control group and the H1299-negative control group (P<0.05), the average tumor weight of H1299 siRNA-1 group was significantly lower than those of H1299-control group and H1299-negative control group (P<0.05), tumor cell growth marker Ki-67 in the H1299 siRNA-1 group showed weak positive, and Ki-67 in the H1299-control group and H1299-negative control group showed positive. The result of qRT-PCR analysis showed that the mRNA expression level of p21 in H1299 siRNA-1 group (2.57±0.45) was higher than those in H1299 control group (1.00±0.00, P=0.001) and H1299 siRNA-NC group (1.52±0.37, P=0.009). The result of western blotting analysis also showed that the expression of p21 protein level in H1299 siRNA-1 group increased. Conclusions: The expression of ultraconserved long non-coding RNA uc.77 is elevated in lung cancer cell lines and lung cancer tissues. Silencing the expression of ultraconservative long noncoding RNA uc.77 can inhibit tumor growth, and blocking uc.77 expression may be a potential therapeutic target for lung cancer.

[Efficacy and safety of omalizumab in patients with refractory allergic asthma: a meta-analysis].

Objective: To evaluate the efficacy and safety of omalizumab in patients with refractory allergic asthma using meta-analysis. Methods: We searched databases including PubMed, Web of Science, Embase and the website of ClinicalTrials. gov registry for randomized controlled trials (RCTs), using the search terms: ("anti-IgE" OR "anti-immunoglobulin E" OR "anti-IgE antibody" OR "omalizumab" OR "rhuMAb-E25" OR "Xolair") AND ("allergic asthma"). The time was up to September 19th 2020. Review Manager 5.4 software and Stata16 software were used to calculate pooled RR or WMD, perform heterogeneity test, and assess publication bias. Results: Fifteen RCTs with 6 316 patients in total (omalizumab, n=3 469; placebo, n=2 847) met our selection criteria. Comparing with placebo, omalizumab reduced the risk of asthma exacerbations during both stable-inhaled corticosteroid (ICS) phase (RR=0.69, 95%CI: 0.63-0.75, P<0.001; I2=39.0%, P=0.090) and ICS-reduction phase (RR=0.55, 95%CI: 0.46-0.66, P<0.001; I2=41.0%, P=0.180), reduced emergency visits (RR=0.53, 95%CI: 0.38-0.73, P<0.001; I2=0, P=0.420), made a significant reduction in dosage of ICS (RR=1.35, 95%CI: 1.25-1.45, P<0.001; I2=22.0%, P=0.280) and even withdrew from ICS completely (RR=1.80, 95%CI: 1.41-2.31, P<0.001; I2=57.0%, P=0.070). Omalizumab significantly improved asthma-related quality of life (RR=1.81, 95%CI: 1.51-2.17). The use of rescue bronchodilators was significantly reduced in the omalizumab group (RR=0.78, 95%CI: 0.67-0.92) but there was no significant difference in the dosage of rescue bronchodilators (puff per day) (WMD=-0.32, 95%CI: -0.77-0.13). Patients taking omalizumab did not increase the frequency of any adverse events (RR=1.01, 95%CI: 0.98-1.03) and serious adverse events (RR=0.89, 95%CI: 0.74-1.06). Conclusions: Omalizumab is an ideal adjunctive treatment for refractory allergic asthma with good efficacy and safety. Further randomized controlled trials are needed to determine the appropriate duration of treatment.

[Evaluation of the level of carotid bifurcation and the morphology of extracranial internal carotid artery in patients with carotid stenosis by color doppler ultrasound and digital subtraction angiography].

Objective: To evaluate the value of color Doppler ultrasound and digital subtraction angiography (DSA) in evaluating the level of carotid bifurcation and the morphology of extracranial internal carotid artery in patients with atherosclerotic carotid stenosis. Methods: The carotid artery examination data of 186 patients with atherosclerotic carotid stenosis who underwent carotid DSA and color Doppler ultrasound in Shanghai Changzheng Hospital from July 2017 to June 2019 were retrospectively analyzed, including 154 males and 32 females, with ages ranging from 36 to 84 (66±8) years old. The correlation between the position of carotid bifurcation and the level of cervical spine, the distance from the position of carotid bifurcation to mandibular angle, the correlation of the level of bifurcation with the length of neck, and the incidence of carotid distortion were analyzed. Results: DSA showed that the most common position of carotid bifurcation was at C3 level on the left [37.3% (56/150)], and at C3-C4 level on the right [33.6% (42/125)], and the highest position was at C2 level on the left, and at C2-C3 levels on the right, while the lowest level on both sides was at C5 level. The incidence of high bifurcation of left carotid artery (C3 and above) was 46% (69/150), which was higher than that of right carotid artery [21.6% (27/125), P<0.001]. The incidence of high carotid bifurcation in men and women was 33.2% (76/229) and 43.5% (20/46), respectively, with no significant difference (P = 0.182). Carotid ultrasound showed that the distance between the left carotid bifurcation and the mandibular angle was (3.0±1.3) cm, which was shorter than that on the right [(3.4±1.2) cm] (P<0.001). The distance between carotid bifurcation and mandibular angle in men and women was (3.2±1.2) cm and (3.3±1.0) cm, respectively, with no significant difference (P = 0.093). There was no significant correlation between carotid bifurcation level and carotid length (right: r = 0.02, P = 0.091; left: r = 0.01, P = 0.927). The incidence of carotid artery distortion was 28.1% (9/32) in women and 15.6% (24/154) in men, with no significant difference (P = 0.091). The incidence of right carotid artery distortion in high bifurcation group was 59.3% (16/27), which was higher than that in non-high bifurcation group [3.1% (3/98)] (P<0.001). Likewise, the incidence of left carotid artery distortion in high bifurcation group was 30.4% (21/69), which was higher than that in non-high bifurcation group [2.5% (2/81)] (P<0.001). Conclusions: The bifurcation position of left carotid artery in patients with atherosclerotic carotid stenosis is higher than that of the right. Patients with high bifurcation of carotid artery are more likely to be complicated with carotid distortion. Preoperative color doppler ultrasound combined with DSA can evaluate the distortion of extracranial carotid artery, thereby providing reference for the selection of surgical methods.

[The new classification and treatment of neck hemorrhage].

Neck is an important and complex region of the human body. Once injury occurs, it often leads to a high mortality rate and complication rate, among which vascular injury and massive hemorrhage are the main causes. However, due to the particularity of neck structure, there is a lack of effective control methods for cervical vascular hemorrhage, and there is still no consensus on the diagnosis and treatment of cervical vascular hemorrhage. Combined with the newest researches, this paper tries to explore and summarize the experience of the new classification and management principle of vascular massive hemorrhage.

[Analysis of types and treatment methods of cervical massive hemorrhage].

Objective: To summarize the classification and clinical treatment experience of cervical massive hemorrhage in multiple centers. Methods: From April 2012 to October 2020, clinical data of 42 patients with cervical massive hemorrhage were retrospectively analyzed, including 27 cases from Shanghai Changzheng Hospital, 7 cases from Hunan Provincial People's Hospital, 4 cases from Longkou People's Hospital and 4 cases from Laizhou People's Hospital. According to bleeding position (P), bleeding vessel (V), cerebral blood supply (C), and the presence or absence of associated injury (A), 42 patients were classified as "PVCA", and summarize the methods of pre-hospital emergency and in-hospital treatment based on the "ABC" treatment principles: airway rebuild (A), effective arterial hemostasis and bleeding stop (B), and cerebral blood flow reconstruction within the time window (C). Results: Within the 42 cases of cervical massive hemorrhage, there were 3 cases of type P1 (below cricoid cartilage), 28 cases of type P2 (cricoid cartilage-mandibular angle), 11 cases of type P3 (mandibular angle-skull base); 22 cases of type V1 (arterial hemorrhage), 11 cases of type V2 (main venous hemorrhage), 7 cases of type V3 (simple superficial vein or small artery hemorrhage), 2 cases of type V4 (mixed arteriovenous hemorrhage); 5 cases of type C0 (no symptoms of cerebral ischemia and neurological dysfunction), 33 cases of type C1 (transient cerebral ischemia without sensory disturbance), 4 cases of type C2 (symptoms of cerebral ischemia and neurological dysfunction); 39 cases of type A0 (no other system damage was involved) and 3 cases of type A1 (combined with other system damage). All 42 patients received operations, 25 patients received open surgery of vascular reconstruction+hematoma/foreign body removal (7 cases of vascular ligation, 14 cases of direct suture repair, 4 cases of vascular interposition), 17 patients received hybrid surgery (carotid angiography+covered stent repair+hematoma/foreign body removal). The surgical technique success rate the was 100%. All the hemorrhagic shock was corrected, hematoma compression was relieved, and the symptoms of cephalic ischemia were improved. There were 4 cases of local cranial nerve injury, 1 case of incision hematoma and 6 cases of postoperative hyper perfusion. During the average 14.3 months follow-up, there was no operation related myocardial infarction, stroke or death, no re-rupture or re-dissection, and 50% asymptomatic restenosis was found in 1 case one year after received covered stent endovascular repair. Conclusion: Based on the "PVCA" classification and "ABC" treatment principle, it is safe and effective to rescue cervical massive hemorrhage.

[Genotyping analysis of norovirus infectious diarrhea clusters in Songjiang district, Shanghai from 2017 to 2019].

Objective: We aimed to analyze the the genotyping of norovirus infectious diarrhea epidemic in Songjiang district, Shanghai, and explored the experience in handling the epidemic to provide a scientific basis for formulating prevention and treatment strategies. Methods: The epidemiological data and related samples of 69 outbreaks of infectious diarrhea caused by norovirus was collected from 2017 to 2019 in Songjiang district, Shanghai. Sequencing and type identification were performed by the method of gene sequencing for the junction region of Norovirus ORF1 and ORF2. Results: From 2017 to 2019, 69 outbreaks of norovirus infections diarrhea were reported in Songjiang district, Shanghai. A total of 1 767 samples were tested, including 619 case samples (positive rate 19.9%), 343 practitioner samples (positive rate 1.1%), 505 environmental samples (positive rate 0.5%) and 300 food samples (not detected). 141 sequences were obtained, and the genotype analysis showed that the genotype that mainly caused infectious diarrhea in 2017 and 2018 was GII.P16-GII.2 (50.98%, 26/51). In 2019, the genotypes that mainly caused infectious diarrhea were GII.P16-GII.2 (13.73%, 7/51) and GII.Pe-GII.4 (9.80%, 5/51). Conclusion: The main genotype of the 69 outbreaks of nororirus infectious diarrhea epidemic in Songjiang district, Shanghai from 2017 to 2019 was GII.P16-GII.2, which showed obvious peaks in spring, autumn and winter. There were more infections in kindergartens and schools. The surveillance of norovirus infection should be strengthened.

[Clinical observation and analysis on the effect of orthokeratology in myopic anisometropic children].

Objective: To evaluate the clinical effects of orthokeratology lens on children with myopic anisometropia. Methods: Retrospective case series study. The data of 226 myopic anisometropia children, (10.83±1.56)years old, including 95 males and 131 females, fitted with orthokeratology(OK) lens in Beijing Tongren Hospital from June 2017 to June 2019 were collected. According to the lens wearing condition and baseline anisometropia, they were divided into four groups: group A1 with an average age of (10.68±1.66) years (bilateral OK lens wearing with low anisometropia, 1.0 D≤SE difference<2.5 D, 50 males and 61 females), group A2 with an average age of (11.24±1.38) years (bilateral OK lens wearing with moderate and high anisometropia, SE difference≥2.5 D, 10 males and 23 females), group B1 with an average age of (10.79±1.51) years (unilateral OK lens wearing with low anisometropia, 1.0 D≤SE difference<2.5 D, 17 males and 21 females) and group B2 with an average age of (10.97±1.60) years (unilateral OK lens wearing with moderate and high anisometropia, SE difference≥2.5 D, 18 males and 26 females). After wearing OK lens for one year, the changes of axial length(AL) and AL difference were observed and statistically analyzed. Results: (1) AL changes: after wearing OK-lens for one year, AL of each eye increased. In group A1, the AL of the more myopic eyes and the less myopic eyes increased by (0.20±0.21) mm and (0.24±0.22) mm respectively, and the difference was statistically significant (t=-3.208, P=0.002); in group A2, the AL growth of the more myopic eyes and the less myopic eyes were (0.04±0.11) mm and (0.17±0.14) mm, and the difference was statistically significant (t=-5.545, P<0.001). In group B1, the AL elongation of the more myopic eyes and the less myopic eyes were (0.14±0.21) mm and (0.39±0.23) mm, and in group B2, the AL growth of the more myopic eyes and the less myopic eyes were (0.11±0.14) mm and (0.54±0.24) mm, with statistically significant differences(t=-6.533, -11.643; all P<0.001). There was a linear correlation between AL elongation and age of the more myopic eyes and the less myopic eyes in group A1(corrected R2=0.208, 0.237) and group A2 (corrected R2=0.169, 0.360). There was no linear correlation of the more myopic eyes and the less myopic eyes between AL change and age or baseline myopia in group B1 (F=0.514, 1.205;P=0.602, 0.312) and group B2 (F=0.841, 0.056; P=0.439, 0.946). (2)Change of AL difference: after wearing OK lens for one year, the changes of AL difference in groupA1, A2, B1 and B2 were (-0.04±0.14) mm,(-0.13±0.13) mm,(-0.26±0.24) mm and (-0.43±0.25) mm, and the decrease of AL difference in moderate and high anisometropia groups were greater than that in low anisometropia groups (t =-3.211, -3.180; P=0.002, 0.002).There was a linear correlation between the reduction of AL difference and baseline anisometropia in group A1, A2 and B2 (corrected R2=0.099, 0.149, 0.230), and there was no linear relationship between the decrease of AL difference and the baseline anisometropia in group B1 (F=0.014, P=0.908). Conclusions: Orthokeratology could effectively control the progression of myopia and to treat anisometropia. The effect of myopia control was better in the older binocular OK lens wearers, and for the patients with greater baseline anisometropia, the treatment effect of anisometropia was better.

Functional divergence of white genes in Henosepilachna vigintioctopunctata revealed by RNA interference.

Henosepilachna vigintioctopunctata is a serious pest of Solanaceae and Cucurbitaceae in many Asian countries. RNA interference (RNAi) can effectively reduce transcript abundance in this beetle, offering opportunities to explore the biological function of specific genes. The white gene encodes a half-type ATP-binding cassette transporter that plays an essential role in tryptophan, guanine and uric acid transport across membranes. Mutations that disrupt the function of white are known to cause eye pigmentation phenotypes in many insect species. Here, we found evidence for five white gene paralogues present in H. vigintioctopunctata transcriptome datasets sequenced from a range of developmental stages. We individually knocked down each of the five white genes through the injection of corresponding double-stranded RNAs (dsRNAs) to the fourth-instar larvae to determine whether functional divergence has occurred. We found that injecting 1 µg dswhite3 caused compound eye colour of pupae and adults to develop as red/brown and brown, respectively, compared with black eyes in control beetles. Injection of 2 µg dswhite3 increased RNAi efficacy and produced a clearer eye colour phenotype. At both doses, the ocular diaphragm (a ring of black pigment surrounding each eye) did not change in the white3 RNAi hypomorphs. Moreover, our data revealed that injection of dswhite2 at the fourth-instar larval stage impaired the climbing ability of both male and female adults. Our results confirmed, for the first time, functional divergence of duplicated white genes in an insect species.

Pain severity and use of analgesic medication in adults with atopic dermatitis: a cross-sectional study.

BACKGROUND: Adult patients with atopic dermatitis (AD) report skin pain, but the relationship with disease severity, anatomical location and use of pain medication is unclear. OBJECTIVES: To examine pain in adults with AD. METHODS: We performed a cross-sectional study of nationwide healthcare data and survey data from the Danish Skin Cohort. In total, 3208 randomly selected adults from the general population and 3834 adults with a dermatologist-verified diagnosis of AD present in adulthood were included. Patient-Oriented SCORing Atopic Dermatitis determined AD severity, and numerical rating scales estimated the severity of pruritus and skin pain. Complete information on the use of analgesic medication was obtained from the Danish nationwide prescription registry. RESULTS: Respectively, 6·8%, 55·5%, 34·0% and 3·7% of the AD cohort reported that they were asymptomatic, or had mild, moderate or severe disease at the time of assessment. Skin pain was positively associated with AD severity and itch. Higher skin pain scores were observed in plantar, chest and palmar areas. Use of pain medication was not increased in patients with AD. CONCLUSIONS: Patients with AD did not display increased use of pain medication, but few had severe disease. The close relationship observed between itch and pain highlights the potential benefits of established AD treatments to also reduce skin pain in AD. What's already known about this topic? There is increased awareness about skin pain being a significant burden of atopic dermatitis (AD). What does this study add? We found that skin pain is increased with AD severity and itch. The comparable use of pain medication in patients with AD and controls suggests that dermatological treatments reduce skin pain.

Comparable efficacy and safety of brodalumab in obese and nonobese patients with psoriasis: analysis of two randomized controlled trials.

BACKGROUND: Obesity is associated with psoriasis and negatively affects response to therapy. OBJECTIVES: To evaluate the efficacy and safety of brodalumab in nonobese vs. obese patients with psoriasis. METHODS: This is a post hoc analysis of the prospective, phase III, multicentre, randomized, placebo- and active-comparator-controlled AMAGINE-2 and AMAGINE-3 trials, in which patients were randomized to treatment with brodalumab 210 mg every 2 weeks, ustekinumab or placebo for a 12-week induction phase. At week 12, patients who received brodalumab 210 mg every 2 weeks continued brodalumab, those treated with ustekinumab continued ustekinumab, and those who received placebo switched to brodalumab 210 mg every 2 weeks. Patients were categorized by body mass index (BMI) category (< 30 or ≥ 30 kg m-2 ) and efficacy was evaluated using the physician-rated Psoriasis Area and Severity Index and static Physician's Global Assessment instruments. RESULTS: In total, 281 of 687 patients (40·9%) were obese. Skin clearance was comparable across BMI subgroups in brodalumab-treated patients. Psoriasis Area and Severity Index 100% improvement rates in nonobese and obese patients at week 12 were 54·1% and 49·5%, respectively, and at week 52 they were 72·6% and 64·8%, respectively. Week 12 ustekinumab responses were lower than brodalumab responses and were 6-17% lower in obese than in nonobese patients. No appreciable differences in overall safety were observed between nonobese and obese patients. CONCLUSIONS: The efficacy and safety of brodalumab did not differ between patients with moderate-to-severe psoriasis who had a BMI < 30 kg m-2 or a BMI ≥ 30 kg m-2 .

Risk of tuberculosis reactivation during interleukin-17 inhibitor therapy for psoriasis: a systematic review.

Immunosuppressive therapies, effective in treating inflammatory disorders such as psoriasis, increase the risk of serious infections, such as tuberculosis (TB). For example, tumour necrosis factor (TNF)-alpha inhibitors significantly increase the risk of TB reactivation in patients with latent TB infection (LTBI), which has led clinicians to routinely test for TB prior to initiation of these medications. This protocol has since extended to other, newer immunomodulatory therapies for psoriasis, such as interleukin (IL)-17 inhibitors, including secukinumab, ixekizumab and brodalumab. We conducted a systematic review to examine whether there is any evidence that IL-17 inhibitor therapy for psoriasis increases the risk of TB reactivation. Using PubMed and EMBASE, our literature search resulted in 139 total articles. After manually reviewing each article for the discussion of IL-17 inhibitors for psoriasis, with data originating from clinical trials, and assessment for incidence of TB reactivation, 23 articles met the full inclusion criteria for our review. Overall, we found no cases of TB reactivation in patients treated with IL-17 inhibitors for psoriasis. This suggests that IL-17 inhibitors may be safely used in psoriasis patients with LTBI who receive appropriate LTBI treatment. However, long-term real-world studies are warranted to further evaluate this risk.

[Clinical application of three cases of transcarotid artery revascularization].

Objective: To investigate the surgical indications, preoperative evaluation, technical points, perioperative management and effect of transcarotid artery revascularization (TCAR) in the treatment of carotid stenosis. Methods: From March to April 2019, three patients with carotid stenosis undergoing TCAR in the Second Affiliated Hospital of Naval Military Medical University. With the common carotid artery approach, under the protection of the carotid-femoral vein reverse blood flow, the balloon dilatation of the internal carotid artery stenosis and stent implantation to achieve the purpose of carotid revascularization.The patient's general condition, preoperative evaluation, intraoperative operation, postoperative management and complications were recorded in detail. The clinical safety, efficacy and efficacy of TCAR in the treatment of carotid stenosis were evaluated. Results: All three operations were successful, including 2 cases of left carotid artery revascularization and 1 case of right carotid artery revascularization. A total of 3 carotid stents were implanted. The operation time was 65, 59, and 55 min,the intraluminal operation time was 13, 18, and 11 min, the common carotid artery blocked time was 15, 20, and 13 min, the contrast agent was 20, 25,15 ml, respectively. There was no death, no nervous system and other related complications during the perioperative period. Three patients were followed up for 7, 7, and 6 months without death, there were no nervous system diseases and other complications. All patients with ultrasound indicated that the carotid artery stent was patency. Conclusion: TCAR adopts the neuroprotection system of carotid-femoral vein continuous reverse blood flow to prevent transient ischemic attack (TIA) and stroke, and it is a safe and effective treatment for carotid artery stenosis.

Anisotropic dependence of light extraction behavior on propagation path in AlGaN-based deep-ultraviolet light-emitting diodes.

The anisotropic extraction dependence of polarized light on propagation path in AlGaN-based deep-ultraviolet (DUV) light-emitting diodes (LEDs) is investigated by simulations and photoluminescence (PL) measurements. Theoretical calculations based on k⋅p approximation and Monte Carol ray tracing indicate that there are two kinds of polarized sources with different angular distributions in ~280 nm AlGaN-based LEDs, s-polarized (spherical-shaped) and p-polarized (dumbbell-shaped) sources, which have different extraction behaviors. It is found that the total light extraction intensities are improved with decreasing the propagation path, and the lateral surface extraction gradually becomes dominant. Moreover, the extraction intensity of s-polarized light improves more than that of p-polarized light when the propagation path decreases, leading to a greater polarization degree. Polarization-resolved PL measurements show that the polarization degree of extracted light from lateral facet of the AlGaN multiple quantum well sample can be enhanced from 1% to 17% as the average propagation path reduces by 0.6 mm, which is consistent with the simulation results of the anisotropic dependence of light extraction on propagation path. Our results are significant for understanding and modulating the anisotropic extraction behavior of polarized light to realize high efficiency AlGaN-based DUV LEDs.

Silencing chitin deacetylase 2 impairs larval-pupal and pupal-adult molts in Leptinotarsa decemlineata.

Insect chitin deacetylases (CDAs) are carbohydrate esterases that catalyze N-deacetylation of chitin to generate chitosan, a process essential for chitin organization and compactness during the formation of extracellular chitinous structure. Here we identified two CDA2 splice variants (LdCDA2a and LdCDA2b) in Leptinotarsa decemlineata. Both splices were abundantly expressed in larval foregut, rectum, and epidermis; their levels peaked immediately before ecdysis within each instar. In vivo results revealed that the two isoforms transcriptionally responded, positively and negatively respectively, to 20-hydroxyecdysone and juvenile hormone signaling pathways. RNA interference (RNAi)-aided knockdown of the two LdCDA2 variants (hereafter LdCDA2) or LdCDA2b, rather than LdCDA2a, resulted in three negative effects. First, foliage consumption was significantly reduced, larval developing period was lengthened, and larval growth was retarded. Second, chitin contents were reduced, whereas glucose, trehalose, and glycogen contents were increased in the LdCDA2 and LdCDA2b RNAi larvae. Third, approximately 20% of LdCDA2 and LdCDA2b RNAi larvae were trapped within the exuviae and finally died. About 60% of the abnormal pupae died as pharate adults. Around 20% of the RNAi pupae emerged as deformed adults, with small size and wrinkled wings. These adults eventually died within 1 week after molting. Our results reveal that knockdown of CDA2 affects chitin accumulation. Consequently, LdCDA2 may be a potential target for control of L. decemlineata larvae.