[Efficacy of 0.05% cyclosporine A combined with vitamin A palmitate in the treatment of meibomian gland dysfunction-related dry eye].

Objective: To evaluate the efficacy of 0.05% cyclosporine A eye drops combined with vitamin A palmitate eye gel in the treatment of dry eye associated with meibomian gland dysfunction (MGD). Methods: A single-center, prospective, randomized, parallel controlled trial design was used to include patients diagnosed with MGD-associated dry eye. The patients were randomly divided into three groups and administered with medications binocularly for 12 weeks. The CsA+VA group was given 0.05% cyclosporine A eye drops twice a day and vitamin A palmitate eye gel three times a day. The CsA+HA group was given 0.05% cyclosporine A eye drops twice a day and 0.1% sodium hyaluronate eye drops three times a day. The HA group was given 0.1% sodium hyaluronate eye drops 3 times a day. The OSDI score, tear meniscus height, fluorescein tear break-up time, Schirmer Ⅰ test (without anesthesia), tear film lipid layer thickness, meibomian gland morphology and function examination, and corneal fluorescein sodium staining score were evaluated at baseline, 4, 8, and 12 weeks after the initiation of the treatment, respectively. Results: A total of 120 patients with MGD-related dry eye met the enrollment criteria, but 10 patients were lost to follow-up; 110 patients were finally included for observation, including 36 patients in the CsA+VA group, 38 in the CsA+HA group and 36 in the HA group. The OSDI score, tear meniscus height, fluorescein tear break-up time and meibomian gland secretion of the 3 groups were significantly improved. At the 12th week of the treatment, the differences of the CsA+VA group [25.45±15.11, (0.30±0.13) mm, (3.72±1.40) s, (5.03±2.52) points] and the CsA+HA group [26.98±16.89, (0.27±0.10) mm, (4.34±1.76) s, (5.11±2.39) points] from the HA group [24.57±11.26, (0.24±0.06) mm, (3.18±1.11) s, (9.11±3.34) points] were statistically significant (P<0.05). Compared with the CsA+HA group [(68.39±26.66) nm], the tear film lipid layer thickness in the CsA+VA group [(72.61±23.65) nm] was significantly increased (P<0.05). In the CsA+VA group, the meibomian gland secretion characters and discharge capacity among patients with severe abnormalities [(6.28±2.59) and (5.89±2.77) points at the 12th week of treatment], moderate abnormalities [(4.27±2.02) and (4.64±2.02) points at the 12th week of treatment] and mild abnormalities [(2.80±0.84) and (2.60±0.55) points at the 12th week of treatment] were significantly different (P<0.05). Conclusion: 0.05% cyclosporine A combined with vitamin A palmitate can significantly improve the symptoms and signs of patients with MGD-related dry eye, especially the tear film lipid layer thickness and the meibomian gland secretion characters and discharge capacity in severe cases.

[Effects of different eye protection methods during head and neck surgery under general anesthesia].

Objective: To compare the protective effects of vitamin A eye gel combined with 3M transparent tape and erythromycin eye ointment combined with 3M transparent tape on the eye surface during head and neck surgery under general anesthesia. Methods: From June to December 2021, a total of 120 patients undergoing elective head and neck surgery under general anesthesia in Beijing Tongren Hospital, Capital Medical University were enrolled. Each participant was randomly received vitamin A eye gel (vitamin A eye, n=60) or erythromycin eye ointment (erythromycin eye, n=60), followed by 3M transparent tape on one eye, and taping 3M transparent tape alone for the other eye. The hand-held slit lamp examination was performed 3 times at before induction of anesthesia, after resuscitation in the post anesthesia care unit (PACU) and 1 day after surgery. The primary outcome was corneal fluorescein sodium staining (CFS) score. Secondary outcomes included symptom assessment in dry eye (SANDE) questionnaire score, basic tear secretion test (Schirmer I test, SIt), break-up time (BUT) and incidence of adverse reactions. Results: Comparison within groups showed that CFS scores were significantly higher in vitamin A eyes and erythromycin eyes at PACU than before induction (P<0.05). Comparison between groups showed that CFS score at PACU in erythromycin eyes (0.62±0.16) was significantly higher than that in vitamin A eyes (0.13±0.01, P=0.007). Compared with before induction, SIt at PACU was significantly increased in the erythromycin eyes [(16.0±1.3) vs (11.4±4.9) mm, P=0.017],and was significantly decreased in vitamin A eyes [(10.2±3.6) vs (12.4±5.5) mm, P=0.046]. The BUT in PACU of erythromycin eyes, vitamin A eyes were (6.4±2.5) s, (6.8±2.1) s, respectively,and were significantly decreased compared with before induction (P<0.05). Comparison between groups showed that there was no significant difference in BUT and SANDE in PACU between two groups (P>0.05). For erythromycin eyes, discomfort symptoms in PACU included viscosity (66.7%, 40/60), conjunctival congestion (21.7%, 13/60), tingling (8.3%, 5/60), blurred vision (58.3%, 35/60). The incidence of these complications in vitamin A eye was 30.0% (18/60), 5.0% (3/60), 0 and 6.7% (4/60), respectively, and all the incidences were significantly higher than those of vitamin A eyes (all P<0.05). Conclusion: For patients undergoing head and neck surgery under general anesthesia, the combination of vitamin A ocular gel and 3M transparent tape is more effective in prevent postoperative ocular surface injury than the combination of erythromycin ointment and 3M transparent tape.

[Focus on the diagnosis and treatment of blepharokeratoconjunctivitis in children].

Blepharokeratoconjunctivitis, (BKC) is a common ocular surface chronic inflammatory disease in children. It can cause eye irritation or even visual impairment. At present, the etiology of BKC in children is not clear and relevant studies are in the initial stage, consequently, there has not been an authoritative applicable expert consensus in China. Compared with adults, the clinical manifestations of pediatric patients are often atypical, coupled with the lack of understanding, so inadequate diagnosis and treatment are still exist in pediatric BKC. This article reviews the etiology, diagnosis and treatment status, clinical characteristics, standardized diagnosis and treatment of pediatric BKC, in order to arouse the attention of ophthalmologists.

[Mechanical circulatory support combined with immunomodulation treatment for patients with fulminant myocarditis: a single-center real-world study].

Objective: To investigate the relationship between the mechanical circulatory support (MCS) combined with immunomodulation and the prognosis of patients with fulminant myocarditis. Methods: This is a retrospective study. A total of 88 patients with fulminant myocarditis admitted to Dongguan Kanghua hospital from Aug. 2008 to Dec. 2020 were included. Medical histories, results of laboratory tests, treatment regimens and clinical outcomes of these patients during their hospitalization were collected from the medical record system. According to the treatment methods, the patients were divided into MCS+immunomodulation group (38 cases), MCS group (20 cases) and traditional treatment group (30 cases). Patients in the MCS+immunomodulation group received intra-aortic balloon pump (IABP) or IABP combined with extracorporeal membrane oxygenation (ECMO) and immunoglobulin or glucocorticoid. Patients in the MCS group only received mechanical circulatory support. Patients in the traditional treatment group received neither mechanical circulatory support nor immunomodulatory therapy, and only used vasoactive drugs and cardiotonic drugs. The in-hospital mortality and length of stay were compared among the three groups. Results: A total of 88 patients with fulminant myocarditis aged (35.0±10.8) years were included, and there were 46 males (52.3%). The mortality of MCS+immunomodulation group (7.9% (3/38) vs. 56.7% (17/30), P=0.001 2) and MCS group (30.0% (6/20) vs. 56.7% (17/30), P=0.002 8) were lower than that of traditional treatment group. Compared with the MCS group, the in-hospital mortality in the MCS+immunomodulation group was lower (P=0.005 4). The most common cause of death was multiple organ dysfunction syndrome (MODS). The constituent ratios of death in MCS+immunomodulation group, MCS group and traditional treatment group were 3/3, 4/6 and 12/17, respectively. The incidence of MODS in the MCS group (20% (4/20)) and the traditional treatment group (40% (12/30)) was significantly higher than that in the MCS+immunomodulation group (7.9% (3/38)) (both P<0.01). In discharged patients, the hospitalization time of MCS+immunomodulation group was shorter than that of traditional treatment group ((13.4±5.5)d vs. (18.5±7.4)d, P<0.05) and MCS group ((13.4±5.5)d vs. (16.9±8.5)d, P<0.05). Conclusion: MCS combined with immunomodulatory therapy is associated with lower in-hospital mortality and shorter hospital stay in patients with fulminant myocarditis.

Silencing of a putative alanine aminotransferase (ALT) gene influences free amino acid composition in hemolymph and fecundity of the predatory bug, Cyrtorhinus lividipennis Reuter.

In Asian rice systems, Cyrtorhinus lividipennis Reuter is an important predator that preys on rice planthopper eggs and young nymphs, as a primary food source. Alanine aminotransferase (ALT) acts in many physiological and biochemical processes in insects. We cloned the full-length complementary DNA of C. lividipennis ClALT. Expression analysis showed higher expression in the fat body and midgut compared to other tissues. It is expressed in all C. lividipennis developmental stages and at least four organs. Silencing of ClALT by RNA interference significantly decreased the ClALT enzyme activity and ClALT expression compared to dsGFP-treated controls at 2 days after emergence (DAE). Silencing of ClALT influenced free hemolymph amino acid compositions, resulting in a reduction of Aspartic acid (Asp) and Alanine (Ala) proportions, and increased Cysteine (Cys) and Valine (Val) proportions in females at 2 DAE. dsClALT treatments led to decreased soluble total protein concentrations in ovary and fat body, and to lower reduced vitellogenin (Vg) expression, body weight, and the numbers of laid eggs. The double-stranded RNA viruse treatments also led to prolonged preoviposition periods and hindered ovarian development. Western blot analysis indicated that silencing ClALT also led to reduced fat body Vg protein abundance at 2 DAE. These data support our hypothesis that ClALT influences amino acid metabolism and fecundity in C. lividipennis.

[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.

[The prevalence of allergic conjunctivitis based on outpatients in Baotou area].

Objective: To explore the prevalence and influencing factors of allergic conjunctivitis in Baotou area at different times. Methods: A cross-sectional study was conducted in January 2021, 111 patients with allergic conjunctivitis who were admitted to the Department of Ophthalmology, the Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology in 2020 were selected as the research subjects. The basic information, allergic conditions, living habits and other information of the patients were obtained by self-made questionnaire. The pollen concentration and allergy related indicators(allergic duration and frequency, eye itching score, eye burn score, eye foreign body sensation score, tears score and the total scores) of 2019 and 2020 were analyzed by paired sample t-test. The pollen concentration of 2019 and 2020 were analyzed by Wilcoxon signed rank test. The allergy related indicators of different genders were analyzed by independent sample t-test. The allergy related indicators of different ages were analyzed by one-way analysis of variance. The relationship between the length of wearing masks and the allergy related indicators were analyzed by Spearman correlation analysis. Results: Among the 111 patients with allergic conjunctivitis, 54 were males and 57 were females, ranging in age from 8 to 69 years old, with a median age of 35 years old and an average age of (36.77±13.18) years old. The average pollen concentration in Baotou in 2019 was (125.35±222.64) grains/1 000 square millimeter, and the average pollen concentration in Baotou in 2020 was (107.38±137.29) grains/1 000 square millimeter. There was no significant difference in pollen concentration between the two years(Z=-0.178, P=0.859). The severity of allergic indicators in all patients in 2020 is significantly lower than in 2019(t values were 4.701,3.587,2.582,3.661,4.444,2.784,2.555,3.886,respectively, with P<0.05). The severity of allergic indicators in male patients is lower than that of female patients (t values were -1.558, -1.257, -3.41, -3.085, -2.335, -2.897, -2.652, -4.124, respectively). The prevalence of allergic conjunctivitis dose not vary significant with age (P values were 0.504, 0.095, 0.499, 0.265, 0.284, 0.655, 0.421, 0.976, respectively). In 2020, the average time that patients wear masks is (6.55±3.28) h/d, and there is a correlation with the difference in allergy duration (r=0.191, P=0.045). Conclusion: The severity of allergic conjunctivitis in Baotou in 2020 was significantly improved compared with that in 2019, which may be related to masks wearing.

[Insular infraorbital neurovascular pedicle labial salivary gland transplantation for severe dry eye: a case report].

A 52-year-old male presented to Beijing Tongren Hospital with a 5-year history of bilateral dry eyes. He had been diagnosed with Steven-Johnson syndrome due to allergy to cold medication. On examination, the Schirmer I test value was 0 mm, the tear break-up time was 0 s, and corneal fluorescein staining showed corneal epithelial erosion with partial fusion in both eyes. The clinical diagnosis was dry eyes (severe) and Steven-Johnson syndrome. No significant effect was observed after use of artificial tears and anti-inflammatory eye drops and tear punctal embolization. Then an insular infraorbital neurovascular pedicle labial salivary gland transplantation was performed in the right eye. During the 1-year postoperative follow-up, the symptoms and signs were significantly improved in the operated eye, and the surgical results were satisfactory. (Chin J Ophthalmol, 2021, 57: 946-948).

[A special on epidemic prevention and control: precautions in ophthalmic practice in the prevention and control of the novel coronavirus pneumonia epidemic].

This article was published ahead of print on the official website of Chinese Journal of Ophthalmology on March 2, 2020. Prevention and control of novel coronavirus pneumonia is now the top priority, and the protection of the eyes in the fight against the epidemic has also been an issue of great concern. Based on the latest progress made in basic and clinical research and practical experience in epidemic prevention and control, this article delivers objective guidance on whether the eye is a route of transmission of novel coronavirus infection, the precautions that should be taken by ophthalmologists in clinical practice during the epidemic, the novel coronavirus infection in the eyes and its clinical manifestation, and the public health education on eye protection, so as to provide valuable evidence for the scientific prevention and control of the epidemic and developing targeted countermeasures. (Chin J Ophthalmol, 2020, 56: 330-332).

[Preliminary observation on the treatment of primary pterygium with modified conjunctival transplantation and amniotic membrane transplantation combined with use of interferon eye drops].

Objective: To observe the clinical effect of modified conjunctival transplantation and amniotic membrane transplantation combined with use of interferon (IFN) alpha-2b eye drops in the treatment of primary pterygium. Methods: This was a prospective case-control study. Patients with primary pterygium were treated from June 1, 2018 to December 31, 2018 in the Department of Ophthalmology, Beijing Tongren Hospital, and they were divided into two groups (the experimental group and the control group) by the method of randomized block design. Patients in the experimental group received modified conjunctival transplantation and amniotic membrane transplantation combined with use of IFN alpha-2b eye drops, while patients in the control group received pterygium resection combined with conjunctival autograft transplantation. The pterygium type and size were observed before operation, while visual acuity, intraocular pressure and anterior segment details were recorded either. The follow-up was done at 1 week, 2 weeks, 1 month, 3 months, 6 months and 12 months after operation. The visual acuity, corneal epithelial defect, and pterygium recurrence were observed. All data in this manuscript are enumeration data, the expected frequency of pterygium type distribution in the two groups was more than 5, and the chi square test was used, fisher's exact test was used to compare the other data between the two groups. Results: Seventy patients (77 eyes) with pterygium were in this study, including 30 males and 40 females, aged from 50-70 years old. There were 35 cases (38 eyes) in the experimental group and 35 cases (39 eyes) in the control group. 12 months after operation there were 54 cases (60 eyes) including 28 cases (30 eyes) in the experimental group and 26 cases (30 eyes) in the control group with complete data. The corneal epithelium defects of 1 eye in each group was repaired within 7-14 days after operation, and the rest eyes were completely repaired within 7 days after operation. There was no significant difference in the distribution of corneal epithelial healing between the two groups (P= 1.00). There was no significant difference between the two groups in the number of eyes distribute with decreased visual acuity (2 eyes in each group), stable visual acuity (15 eyes in the experimental group and 23 eyes in the control group), and improved visual acuity (13 eyes in the experimental group and 5 eyes in the control group) (P=0.053). There was no recurrence in the two groups at 12 months after surgery, and there was no significant difference between the two groups in the number of patients with conjunctival hyperplasia of grades 1, 2 and 3 (P=0.405). Conclusions: Modified conjunctival transplantation and amniotic membrane transplantation combined with use of IFN alpha-2b eye drops got low recurrence rate for primary pterygium and less damage to the healthy conjunctival tissue. This combined treatment strategy provides a new choice for the treatment of pterygium. (Chin J Ophthalmol, 2020, 56: 768-773).

[Real-world study of paritaprevir/ritonavir-ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in China].

Objective: To evaluate the real-world safety and curative effect of ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in non-cirrhotic or compensated cirrhotic patients. Methods: A real-world research method was adopted, and the research was conducted at three medical centers of mainland China. Non- cirrhotic or compensated cirrhotic patients with HCV genotype 1b infection who were initially treated with IFN/PEG-IFN-alpha combined with ribavirin, and ombitasvir combined with dasabuvir for 8 or 12 weeks were taken. Sustained virological response (SVR) and the incidence of adverse events during treatment and follow-up were evaluated after 12 weeks of drug withdrawal at OBV/PTV/r 25/150/100mg once daily and DSV 250mg, twice daily. Median and range were used for description of non-normally distributed data. Results: 80 cases of GT1b were included in this study. Of these 88.8% (71/80) were newly diagnosed, 12.5% (10/80) were compensated cirrhotic, 97.5% (78/80) received 12 weeks treatment, and 2.5% (2/80) received 8 weeks treatment. The rate of HCV RNA negative at EOT (end of treatment) was 100% (64/64). A total of 67 patients completed the treatment within 12 weeks, and 43 patients returned to the hospital for further consultations, and SVR12 was 100%(43/43). No patient discontinued the drugs because of an adverse event during treatment. Conclusion: In the real world, Ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in China has 100% rates of EOT and SVR12 with well- tolerability and safety.

[Emerging strategies for the treatment of Meibomian gland dysfunction].

Meibomian gland dysfunction (MGD), as a chronic,diffuse Meibomian gland disease,is one of the most common ophthalmological clinical diseases. Symptoms can be mild,such as ocular discomfort, but severe cases resulting in ocular surface damage could affect patients' visual function. Moreover,with the absence of a thorough examination of eyelid status and Meibomian gland prior to ocular surface surgery, it could cause severe postoperative complications. As a usual but easily overlooked disease, MGD and its associated ocular surface diseases have drawn greater attention,on the other hand,some emerging therapies,in addition to the clinically recognized treatments, provided doctors with more effective treatments at their disposal,and plenty of research achievements have been published. This article emphasizes on new physical approaches in the treatments of MGD and its associated ocular surface diseases. (Chin J Ophthalmol, 2019,55:465-468).

[Clinical observation of autologous simple limbal epithelial transplantation for unilateral limbal stem cell deficiency].

Objective: To discuss effect of autologous simple limbal epithelial transplantation (SLET) performed for unilateral limbal stem cell deficiency (LSCD). Methods: Retrospective case study. In this retrospective study, records of 7 patients (7 eyes) who had undergone autologous SLET for unilateral LSCD, with a minimum of 6 months of follow-up, were reviewed. Demographic details, etiology of LSCD, duration between ocular burn and SLET, prior surgery performed, presence or absence of symblepharon, pre-and post-operative visual acuity, and complications were noted. Results: Seven eyes of 7 patients underwent autologous SLET. With a follow-up of 6 months, a completely epithelialised and stable corneal surface was obtained in all recipient eyes. Visual acuity improved in all patients, while none of the eyes developed any complications. Conclusions: Autologous SLET is an effective and safe modality for treatment of unilateral LSCD. Clinical success rates and visual acuity improvement are equal to or better than those reported with earlier techniques. (Chin J Ophthalmol, 2019, 55:923-927).

64Cu-Labeled Gp2 Domain for PET Imaging of Epidermal Growth Factor Receptor.

This purpose of this study is to determine the efficacy of a 45-amino acid Gp2 domain, engineered to bind to epidermal growth factor receptor (EGFR), as a positron emission tomography (PET) probe of EGFR in a xenograft mouse model. The EGFR-targeted Gp2 (Gp2-EGFR) and a nonbinding control were site-specifically labeled with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator. Binding affinity was tested toward human EGFR and mouse EGFR. Biological activity on downstream EGFR signaling was examined in cell culture. DOTA-Gp2 molecules were labeled with 64Cu and intravenously injected (0.6-2.3 MBq) into mice bearing EGFRhigh (n = 7) and EGFRlow (n = 4) xenografted tumors. PET/computed tomography (CT) images were acquired at 45 min, 2 h, and 24 h. Dynamic PET (25 min) was also acquired. Tomography results were verified with gamma counting of resected tissues. Two-tailed t tests with unequal variances provided statistical comparison. DOTA-Gp2-EGFR bound strongly to human (KD = 7 ± 5 nM) and murine (KD = 29 ± 6 nM) EGFR, and nontargeted Gp2 had no detectable binding. Gp2-EGFR did not agonize EGFR nor antagonize EGF-EGFR. 64Cu-Gp2-EGFR tracer effectively localized to EGFRhigh tumors at 45 min (3.2 ± 0.5%ID/g). High specificity was observed with significantly lower uptake in EGFRlow tumors (0.9 ± 0.3%ID/g, p < 0.001), high tumor-to-background ratios (11 ± 6 tumor/muscle, p < 0.001). Nontargeted Gp2 tracer had low uptake in EGFRhigh tumors (0.5 ± 0.3%ID/g, p < 0.001). Similar data was observed at 2 h, and tumor signal was retained at 24 h (2.9 ± 0.3%ID/g). An engineered Gp2 PET imaging probe exhibited low background and target-specific EGFRhigh tumor uptake at 45 min, with tumor signal retained at 24 h postinjection, and compared favorably with published EGFR PET probes for alternative protein scaffolds. These beneficial in vivo characteristics, combined with thermal stability, efficient evolution, and small size of the Gp2 domain validate its use as a future class of molecular imaging agents.

Novel gain of function mutation in the SLC40A1 gene associated with hereditary haemochromatosis type 4.

Here we report the case of a 69-year-old Chinese Han woman who presented with liver cirrhosis, diabetes mellitus, skin hyperpigmentation, hyperferritinaemia and high transferrin saturation. Subsequent genetic analyses identified a novel heterozygous mutation (p.Cys326Phe) in the SLC40A1 gene. This is the first report regarding a SLC40A1 mutation in the Chinese Han population and provides novel clinical evidence for the importance of p.Cys326 in SLC40A1 gene function.

Biomechanical analysis of the longitudinal ligament of upper cervical spine in maintaining atlantoaxial stability.

STUDY DESIGN: In vitro human cadaveric biomechanical study. OBJECTIVES: To investigate the roles of transverse atlantal ligament (TAL) and longitudinal ligament (LL) of the upper cervical spine (UCS) in maintaining atlantoaxial stability. SETTING: China. METHODS: Six intact UCS specimens were harvested and embedded in polymethylmethacrylate. Three-dimensional movements including flexion, extension, right and left lateral bending, and axial rotation, as well as the C1-C2 displacement in flexion (atlantodental interval, ADI), were tested on specimens with the following state sequentially: (1) intact (intact group), (2) TAL transected (TAL group) and (3) TAL and LL disrupted (TAL+LL group) using an electromechanical testing machine. RESULTS: Compared with intact group, the flexion/extension motion range and ADI were significantly higher in TAL group when the loading was 10 N or >100 N. However, no significant differences were detected between the two groups within a range of physiological loading (10-100 N). Similarly, significant differences in right-left lateral bending and axial rotation between TAL and intact groups occurred only when the loading was 150 N. However, when both of the TAL and LL were resected, the atlantoaxial joint showed obvious instability compared with TAL or intact group, which were further demonstrated in the analyses of the three-dimensional movements (significant differences at any loading). CONCLUSION: Within physiological loading range, the LLs have sufficient capacities to maintain the stability of atlantoaxial joint even if there are TAL injuries in atlas fractures.

[Research progress on the effect of common metabolism-related comorbidities on health outcomes and management strategies in patients with chronic hepatitis B].

With the increasing life expectancy and lifestyle changes of patients with chronic hepatitis B (CHB), the significance of comorbidities of chronic non-communicable diseases (NCDs) in disease progression and health prognosis of CHB patients is gaining prominence. This study aims to explore the association between CHB and NCDs comorbidities, focusing on the impact of common metabolism-related diseases, such as metabolic syndrome and diabetes, on the health outcomes of CHB patients. We also summarize studies on integrating the management of comorbidities in CHB patients and provide relevant recommendations for effective management. The findings of this study serve as a foundation for understanding the clinical characteristics and prevalence trends, reducing the disease burden of comorbidities among CHB patients, and establishing a comprehensive and coordinated management system for comorbidities.

Involvement of the ß3-α3 loop of the proline dehydrogenase domain in allosteric regulation of membrane association of proline utilization A.

Proline utilization A (PutA) from Escherichia coli is a membrane-associated trifunctional flavoenzyme that catalyzes the oxidation of proline to glutamate and moonlights as a transcriptional regulator. As a regulatory protein, PutA represses transcription of the put regulon, which contains the genes encoding PutA and the proline transporter PutP. The binding of proline to the proline dehydrogenase active site and the subsequent reduction of the flavin induce high affinity membrane association of PutA and relieve repression of the put regulon, thereby causing PutA to switch from its regulatory to its enzymatic role. Here, we present evidence suggesting that residues of the ß3-α3 loop of the proline dehydrogenase domain (ßα)8 barrel are involved in proline-mediated allosteric regulation of PutA-membrane binding. Mutation of the conserved residues Asp370 and Glu372 in the ß3-α3 loop abrogates the ability of proline to induce functional membrane association. Both in vitro lipid/membrane binding assays and in vivo cell-based assays demonstrate that mutagenesis of Asp370 (D370N/A) or Glu372 (E372A) dramatically impedes PutA functional switching. The crystal structures of the proline dehydrogenase domain mutants PutA86-630D370N and PutA86-630D370A complexed with the proline analogue l-tetrahydro-2-furoic acid show that the mutations cause only minor perturbations to the active site but no major structural changes, suggesting that the lack of proline response is not due to a failure of the mutated active sites to correctly bind the substrate. Rather, these results suggest that the ß3-α3 loop may be involved in transmitting the status of the proline dehydrogenase active site and flavin redox state to the distal membrane association domain.

Magnetic topology changes induced by lower hybrid waves and their profound effect on edge-localized modes in the EAST tokamak.

Strong mitigation of edge-localized modes has been observed on Experimental Advanced Superconducting Tokamak, when lower hybrid waves (LHWs) are applied to H-mode plasmas with ion cyclotron resonant heating. This has been demonstrated to be due to the formation of helical current filaments flowing along field lines in the scrape-off layer induced by LHW. This leads to the splitting of the outer divertor strike points during LHWs similar to previous observations with resonant magnetic perturbations. The change in the magnetic topology has been qualitatively modeled by considering helical current filaments in a field-line-tracing code.

Patients with body mass index ≥25 kg/m2 as a target population for improvement of rate of follow-up duplex venous ultrasound examinations following initial incomplete examinations.

OBJECTIVE: Obesity is highly prevalent and a major risk factor for deep vein thrombosis (DVT) and chronic venous disease. It can also technically limit duplex ultrasound evaluations for lower extremity DVT. We compared the rates and results of repeat lower extremity venous duplex ultrasound (LEVDUS) after an initial incomplete and negative (IIN) LEVDUS in overweight (body mass index [BMI] ≤25-30 kg/m2) and obese (BMI ≥30 kg/m2) patients with those of patients with a BMI <25 kg/m2 to evaluate whether increasing the rate of follow-up examinations in overweight and obese patients might facilitate improved patient care. METHODS: We performed a retrospective review of 617 patients with an IIN LEVDUS study from December 31, 2017 to December 31, 2020. Demographic and imaging data of the patients with an IIN LEVDUS and the frequency of repeat studies performed within 2 weeks were abstracted from the electronic medical records. The patients were divided into three BMI-based groups: normal (BMI <25 kg/m2), overweight (BMI 25-30 kg/m2), and obese (BMI ≥30 kg/m2). RESULTS: Of the 617 patients with an IIN LEVDUS, 213 (34.5%) were normal weight, 177 (29%) were overweight, and 227 (37%) were obese. The repeat LEVDUS rates were significantly different across the three weight groups (P < .001). After an IIN LEVDUS, the rate of repeat LEVDUS for the normal weight, overweight, and obese groups was 46% (98 of 213), 28% (50 of 227), and 32% (73 of 227), respectively. The overall rates of thrombosis (both DVT and superficial vein thrombosis) in the repeat LEVDUS examinations were not significantly different among the normal weight (14%), overweight (11%), and obese (18%) patients (P = .431). CONCLUSIONS: Overweight and obese patients (BMI ≥25 kg/m2) received fewer follow-up examinations after an IIN LEVDUS. Follow-up LEVDUS examinations of overweight and obese patients after an IIN LEVDUS study have similar rates of venous thrombosis compared with normal weight patients. Targeting improving usage of follow-up LEVDUS studies for all patients, but especially for those who are overweight and obese, with an IIN LEVDUS through quality improvement efforts could help minimize missed diagnoses of venous thrombosis and improve the quality of patient care.