A synthetic KLHL20 ligand to validate CUL3KLHL20 as a potent E3 ligase for targeted protein degradation.

Targeted protein degradation (TPD) has risen as a promising therapeutic modality. Leveraging the catalytic nature of the ubiquitin-proteasome enzymatic machinery, TPD exhibits higher potency to eliminate disease-causing target proteins such as oncogenic transcription factors that may otherwise be difficult to abrogate by conventional inhibitors. However, there are challenges that remain. Currently, nearly all degraders engage CUL4CRBN or CUL2VHL as the E3 ligase for target ubiquitination. While their immediate efficacies are evident, the narrowed E3 ligase options make TPD vulnerable to potential drug resistance. In addition, E3 ligases show differential tissue expression and have intrinsic limitations in accessing varying types of disease-relevant targets. As the success of TPD is closely associated with the ability of E3 ligases to efficiently polyubiquitinate the target of interest, the long-term outlook of TPD drug development will depend on whether E3 ligases such as CUL4CRBN and CUL2VHL are accessible to the targets of interest. To overcome these potential caveats, a broad collection of actionable E3 ligases is required. Here, we designed a macrocyclic degrader engaging CUL3KLHL20 for targeting BET proteins and validated CUL3KLHL20 as an E3 ligase system suitable for TPD. This work thus contributes to the expansion of usable E3 ligases for potential drug development.

[Association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40-89 in selected areas of China].

Objective: To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China. Methods: The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function. Results: The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M (Q1, Q3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) µg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95%CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion: Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

[Significance of accurately interpreting the Bielschowsky tilt test in the differential diagnosis of superior oblique muscle paralysis].

Superior oblique muscle paralysis is a common type of vertical rotatory strabismus with various subtypes. Regardless of the subtype, the Bielschowsky tilt test plays a crucial role in the diagnosis of superior oblique muscle paralysis and is often considered a significant criterion for diagnosis and differential diagnosis. However, the sensitivity and specificity of the Bielschowsky tilt test for diagnosing superior oblique muscle paralysis are not 100% due to the mechanism involved. The test is not solely based on extraocular muscle imbalance but also involves reflex pathways of the vestibular system and central nervous system. Consequently, lesions affecting corresponding areas may yield positive results in the Bielschowsky tilt test. Additionally, vestibular and central nervous system lesions can also cause strabismus, leading to a lack of one-to-one correspondence between a positive Bielschowsky tilt test and superior oblique muscle paralysis. Therefore, correctly interpreting the role of the Bielschowsky tilt test in superior oblique muscle paralysis is of paramount importance for the effective clinical management and treatment of associated conditions.

[Clinical characteristics and surgical outcomes in pediatric progressive restrictive strabismus].

Objective: To investigate the clinical features, imaging manifestations, histopathological characteristics, and surgical outcomes in pediatric progressive restrictive strabismus. Methods: A retrospective case series study was conducted, including data from 9 cases (9 eyes) of pediatric progressive restrictive strabismus treated at Tianjin Eye Hospital from June 2017 to October 2022. The study compared the degree of globe protrusion in both eyes, changes in eyelid fissure height during internal and external rotation in the primary gaze, summarized clinical characteristics, and analyzed intraoperative conditions, surgical outcomes and postoperative histopathological results of strabismus correction surgery. Statistical analysis was performed using Wilcoxon signed-rank test and Friedman two-way analysis of variance. Results: All 9 cases involved unilateral onset, with 4 males and 5 females. Three cases affected the right eye, and six affected the left eye. Onset age ranged from 2 to 40 months. The degree of globe protrusion in the affected eyes was 13.00 (12.00, 13.00) mm for the right eye and 12.00 (12.00, 13.50) mm for the left eye, with no statistically significant difference (Z=-1.00, P=0.317). There were no significant changes in eyelid fissure height during internal rotation [8.00 (7.25, 8.00) mm], primary gaze [7.50 (7.00, 8.00) mm], and external rotation [8.00 (7.75, 8.00) mm] in the affected eyes (χ²=1.00, P=0.607). No apparent abnormalities were observed in head CT or MRI scans, serum, or immunological tests. However, orbital CT or MRI scans indicated thickening of different extraocular muscle bellies. Six out of nine cases underwent strabismus correction surgery, and postoperative examination revealed restriction in eye movement despite achieving orthophoria in the primary gaze. Tissue pathology of three cases showed increased collagen fiber proliferation in one, scattered bundles of smooth muscle fibers amid diffuse collagen fiber proliferation in another, and abnormal proliferation of striated muscle fibers with varying diameters, increased paired box (PAX)7-positive satellite cells expressing slow muscle myosin in the third case. Conclusions: Pediatric progressive restrictive strabismus presents with restrictive changes, without significant alterations in globe protrusion and eyelid fissure height. Imaging examinations reveal thickening of the extraocular muscle bellies in the affected eye. Although strabismus correction surgery improves eye position, postoperative eye movement remains restricted. Histopathological findings in some cases show abnormal proliferation of skeletal muscle fibers or collagen fibers.

Assessing hydrological connectivity for natural-artificial catchment with a new framework integrating graph theory and network analysis.

Anthropogenic activities alter the underlying surface conditions and arrangements of landscape features in a drainage basin, interfering with the pollutant (e.g., dissolved nitrogen, phosphorus) transport network configuration and altering the hydrological response. Assessing the impact of anthropogenic activities on hydrological connectivity for natural-artificial catchment is critical to understand the hydrological-driven ecosystem processes, services and biodiversity. However, quantifying this impact at catchment scale remains challenging. In this study, a new framework was proposed to quantify the impact of anthropogenic activities on hydrological connectivity combined with graph theory and network analysis. This framework was exemplified in a natural-artificial catchment of the Yangtze River basin of China. Based on remote sensing and field-investigated data, three transport networks were constructed, including natural transport network (N1), ditch-road transport network (N2), and terrace-dominated transport network (N3), which reflected the different human intervention. The results showed that human intervention improved the connectivity of the nodes and enhanced the complexity of the catchment transport network structure. Anthropogenic activities significantly decreased the hydrological structural connectivity of the catchment. In particular, compared with the N1 network, the critical nodes for hydrological connectivity which were judged by connectivity indexes were reduced by 92.94% and 95.29% in the N2 and N3 network, respectively. Furthermore, the ditch-road construction had a greater impact than terraces in decreasing hydrological structural connectivity at catchment scale. This framework has proven effective in quantifying the hydrological connectivity analysis under different human intervention at the catchment scale and facilitates the improvement of catchment management strategies.

[Morphological study of extraocular muscles in dissociated vertical deviation by magnetic resonance imaging].

Objective: To observe the changes of pulley locations and muscle volumes of extraocular rectus muscles in dissociated vertical deviation. Methods: This was a cross-sectional study. Data was collected from January 2020 to December 2020 in Tianjin Eye Hospital. The pulley locations and muscle volumes of extraocular rectus muscles in DVD patients and healthy volunteers were observed and calculated by continuous coronal MRI scan. One-way ANOVA and independent sample T test were used for statistical analysis. According to the examination results, Groups were divided into A (symmetric DVD), B (asymmetric DVD) and C (healthy volunteers). Data of symmetric DVD patients were divided into dominant eye (A-D) and non-dominant eye (A-nD), while that of asymmetric DVD patients were divided into severe DVD (B-s) and mild DVD (B-m). Volume of 4 rectus muscles and superior oblique muscle were calculated and compared to Group C, respectively. Results: Group A included 5 patients (10 eyes), 2 males and 3 females, aged (22±4) years; Group B included 4 patients (8 eyes), 2 males and 2 females, aged (28±8) years; Group C included 10 patients (20 eyes), including 4 males and 6 females, aged (25±6) years. There was no significant differences in age(F=0.45,P=0.648)or gender(χ2=0.78;P=0.833)among the three groups. There was no significant difference in pulley locations of extraocular rectus muscles between the three groups (FMR=0.52,FLR=0.62,FSR=0.72,FIR=1.16;all P>0.05). Among the four exterocular rectus muscles, the muscle volume of MR [A-D: (562.8±64.4) mm3,A-nD: (560.6±53.2) mm3,B-s: (557.0±48.7) mm3,B-m: (551.5±45.8) mm3], LR [A-D: (519.8±44.5) mm3,A-nD: (511.0±49.4) mm3,B-s: (501.0±35.6) mm3,B-m: (498.3±45.3) mm3] and SR [A-D: (472.8±66.9) mm3,A-nD: (449.4±41.7) mm3,B-s: (433.0±60.8) mm3,B-m: (412.5±54.5) mm3] in group A and group B was higher than that in group C [MR: (423.3±51.9)mm3,LR: (439.7±35.3)mm3,SR: (328.1±36.5)mm3], and the difference was statistically significant (All P<0.05). The inferior rectus muscle volume of dominant eye in group A and mild DVD eye in group B was significantly different from that of healthy volunteers in group C [(453.8±46.8) and (463.0±16.6) vs. (380.4±59.7) mm3, respectively], and the difference was statistically significant (all P<0.05). Conclusions: There are no significant changes in pulley locations of extraocular rectus muscles in patients with symmetric and asymmetric DVD, and the muscle volumes of medial, lateral and superior rectus muscle are greater than those of healthy people. However, the muscle volumes of inferior rectus muscle of dominant eye in symmetric DVD and mild DVD eye are significantly greater.

[Evaluation considerations for using surrogate endpoints in anticancer clinical trials].

The prolongation of patient's overall survival is the accepted as gold standard to prove clinical values of anti-cancer drugs. However, if overall survival is taken as the primary endpoint in clinical trials for cancer types with a relatively good prognosis in the process of new anti-cancer drug research and development, the time to market the drugs will be prolonged due to the long follow-up time. In addition, overall survival is often interfered by confounding factors such as follow-up treatment. Therefore, regulatory agencies have established an accelerated review model using surrogate endpoints for the approval of new anti-cancer drugs, but there are still some problems in the use of surrogate endpoints in cancer clinical trials. From the perspective of new drug review, the authors expounds the key points of confirming and rationally using surrogate endpoints in clinical trials of anti-cancer drugs, which will improve the level of clinical trials of new anti-cancer drugs and accelerate the development of anti-tumor drugs.

[Rethinking the marketing strategy of anti-tumor drugs by single-arm trials supported].

Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.

[The influence of meteorological factors on SARS-CoV-2 transmission: evidence from laboratory and epidemiological studies].

SARS-CoV-2 has infected more than 600 million people worldwide and caused more than 6 million deaths. The emerging novel variants have made the epidemic rebound in many places. Meteorological factors can affect the epidemic spread by changing virus activity, transmission dynamic parameters and host susceptibility. This paper systematically analyzed the currently available laboratory and epidemiological studies on the association between the meteorological factors and COVID-19 incidence, in order to provide scientific evidence for future epidemic control and prevention, as well as developing early warning system.

[Advances in the development of ocular cardiac reflex in extraocular muscle surgery].

Ocular cardiac reflex (OCR) usually occurs in ophthalmic surgery, especially in extraocular muscle(s) surgery. OCR generally can cause sinus bradycardia, arrhythmia, reduced atrial pressure, ventricular tachycardia, ventricular fibrillation, ventricular doublet, dizziness, nausea and other symptoms. Severe cases will appear cardiac arrest, respiratory arrest, etc. Recent studies on the mechanism of OCR and the relationship between surgical operation and anaesthesia in extraocular muscle surgery and the occurrence of OCR are reviewed in this paper in order to reduce the occurrence of OCR and treatment of OCR in extraocular muscle surgery.

[Graded vertical rectus tenotomy for small angle vertical deviation].

Objective: To observe the effectiveness of the graded vertical rectus tenotomy procedure for small-angle vertical deviation. Methods: Retrospective case series study. Twelve patients, including 8 males and 4 females, with an average age of (48±8) years were treated in Tianjin Eye Hospital from January 2017 to December 2019 for diplopia in primary gaze by strabismus surgery. The disease duration was (15±7) months. MRI/CT scan of the orbits and brain was performed to exclude the orbital and craniocerebral diseases. All patients underwent ocular movement examination, with the prism and alternate cover test to detect the deviation angle in primary gaze and the double Maddox test. Based on the results, the posterior segment of the nasal/temporal superior/inferior rectus muscle was operated. The changes of vertical and cyclotorsion deviation angle and the relationship between the vertical rectus graded tenotomy and corrected vertical deviation angle were observed at 1 day after surgery and the last follow-up. The vertical deviation angle was represented by M (Q1, Q3). Friedman test (Bonferroni correction) and linear fitting analysis were used for statistical analysis. Results: The follow-up time of all patients was (7±3) months. The vertical deviation angle in primary gaze before surgery [7.00 (5.25, 7.75) PD] was significantly different from that at 1 day after surgery [1.00 (1.00, 2.00) PD] and the last follow-up [1.50 (1.00, 2.00) PD] (P<0.001, P=0.003). There was no significant difference in postoperative cyclotorsion in all patients. Linear fitting results showed that 50% to 90% vertical rectus tenotomy corrected 5 to 8 PD vertical deviation (R2=0.72; P<0.001). Conclusion: The graded vertical rectus tenotomy procedure can effectively improve the small-angle vertical deviation in primary gaze.

[Characteristics of visual function in children with autism complicated with mental retardation].

Objective: To explore the characteristics of visual function and eye diseases in children with autism spectrum disorder (ASD) and mental retardation. Methods: It was a cross-sectional study. Two hundred and ninety-two cases (584 eyes) of children with ASD combined with mental retardation from 7 special education schools in Chaoyang District of Beijing, including 235 males (80.48%) and 57 females (19.52%); The age ranged from 2 to 18 years old. Subjective far and near vision, near stereoacuity, objective vision, diopter, anterior segment and fundus were examined. In addition, 300 students with normal intelligence level, aged 2 to 18 years, were included as controls. LogMAR was used to record vision examination. Subjective, objective vision and diopter were examined. Mann Whitney U test or Kruskal Wallis H test was used for the data of children with different genders, different age. Results: Among 584 eyes of children with ASD and mental retardation, 272 eyes (47.22%) were ametropia, 260 eyes (45.14%) were astigmatism, 29 eyes (5.03%) were hyperopia, 10 eyes (1.74%) were myopia, and 47 eyes (8.16%) were amblyopia risk factors. Among 292 children, there were 20 cases of strabismus (6.85%), 3 cases of color weakness (1.03%), and 4 cases of external eye abnormalities (1.37%). Two hundred and eleven children completed near stereopsis examination, of which 54 (25.59%) were within 100″ and 157 (74.41%) were within 200″ to 900″. Two hundred and seventy-two eyes with ametropia, 157 eyes (57.72%) needed correction but did not. The median and quartile of subjective and objective logMAR visual acuity were 0.22(0.10, 0.35), 0.10(0.00, 0.22), respectively; There were no significant differences in far visual acuity, near visual acuity, objective visual acuity, diopter, and near stereoacuity between different genders of ASD children with mild or moderate mental retardation (all P>0.05); There was a statistically significant difference in ASD children with mild mental retardation at different age rangs (H=21.453, P<0.001). There was a statistically significant difference in subjective tests such as far visual acuity and near visual acuity, for children with moderate mental retardation (Z=-3.508, -4.503; P<0.001). There was no statistically significant difference in objective visual acuity, diopter and near stereo acuity(all P>0.05). There are 300 healthy children as the control group, with LogMar's subjective far vision is 0.10(0.00, 0.22), and the objective vision is 0.00(0.00, 0.10), diopter 0.25 (-0.25, 0.50) D. Compared with healthy children, ASD children with mental retardation had a significant difference in subjective far vision and objective vision (Z=-8.527, -10.393; P<0.001). There was no significant difference in diopter (Z=-1.274, P=0.203). Conclusions: The subjective and objective visual acuity of children with ASD combined with mental retardation was lower than that of healthy children. The prevalence and uncorrected rate of refractive errors, strabismus, amblyopia and other eye diseases were significantly higher than those of healthy children. Their refractive errors were mainly astigmatism, and the rates of correction and treatment were low.

[Clinical analysis and surgical treatment of atypical acute acquired concomitant esotropia].

Objective: To investigate the clinical characteristics, possible etiology and surgical efficacy of acute acquired concomitant esotropia (AACE) with atypical etiology. Methods: Case-control study. Twelve patients, including 7 males and 5 females, who complained of diplopia and were diagnosed with AACE in Tianjin Eye Hospital from January to December 2019 and underwent surgical treatment were included. The duration of the disease was (8.83±3.71) months. All patients underwent routine ocular examination except amblyopia and ocular organic lesions. MRI examination of the orbits and the brain was performed in all the patients in order to screen orbital and craniocerebral diseases, and patients denied that the existence of common causes of AACE (such as occlusion of one eye, mental or psychological factors, medium to high myopia, etc. during medical examination). The characteristics of the disease, the difference of deviation angle at 33 cm and 5 m, and the changes of deviation angle and stereopsis before and after surgery were analyzed. The forced duction test was performed before operation, and the distance between the sclera margin and the midpoint of the medial rectus muscle attachment was measured and compared with the patients with intermittent exotropia (10 cases) and comitant esotropia (10 cases). Paired sample t-test and one-way analysis of variance were used for statistical analysis. Results: The mean spherical equivalent was (1.70±0.88) D in all AACE patients, and the deviation angle was (22.42±5.82) prism diopter (PD) at 33 cm and (20.00±4.86) PD at 5 m in primary gaze, which were not statistically significant (P=0.371). The force duction test showed no obvious tension or contracture of the medial rectus and no paralysis. In patients with AACE, the horizontal distance from the midpoint of the medial rectus to the limbus was (5.20±0.27) mm, versus (5.30±0.25) mm in intermittent exotropia patients and (5.30±0.31) mm in concomitant esotropia patients. All the differences were not statistically significant (P=0.618). All the patients with AACE had residual esotropia (mean, 3.42 to 6.33 PD) at 6 weeks, 3 months, and 6 months postoperatively, and their stereopsis improved more than before, with no stereopsis in 2 patients before surgery and stereopsis in all 12 patients after surgery. Conclusions: AACE patients with atypical etiology do not have high myopia and hyperopia. There is no significant difference between the distance and near angles. The occurrence of esotropia is related to decompensation of esophoria, which may result in clinical symptoms of diplopia. Conventional surgery can reduce esotropia and restore stereoscopic vision, but there is still a small amount of esophoria after surgery. There is no abnormality in the attachment point of the medial rectus muscle. (Chin J Ophthalmol, 2021, 57: 348-352).

[MRI study of rectus extraocular muscles in concomitant exotropia with small angle vertical deviation].

Objective: To observe the changes of four pulley locations of extraocular rectus muscles and rectus muscle volumes, as well as superior and inferior part ratio of horizontal rectus muscles, in concomitant exotropia with small-angle vertical deviation in primary gaze. Methods: Cross-sectional study. Data was collected from January 2018 to December 2019 in Tianjin Eye Hospital. The pulley position changes and volumes of four extraocular rectus muscles in the coronal position of patients who had concomitant exotropia without vertical deviation (group A) or with small-angle vertical deviation in primary gaze (<5 prism diopter; group B) and normal controls (group C) were observed using MRI, and the changes of the volume ratio of the superior and inferior parts of the horizontal rectus muscle were calculated. One way analysis of variance and Kruskal-Wallis test were used for statistical analysis. Results: There were 19 patients (38 eyes; 10 males, 9 females) aged (30±7) years in group A, ten patients (20 eyes; 4 males, 6 females) aged (27±6) years in group B, and 20 healthy volunteers (40 eyes) in group C. Age and gender distribution were matched among the three groups (all P>0.05). Among the three groups, the pulley locations of the four extraocular rectus muscles were not significantly different (all P>0.05). The medial rectus muscle volume in groups A [(358.6±44.9) mm3; t=6.405, P<0.01] and B [(334.7±35.6) mm3; t=6.025, P<0.01] was significantly smaller than group C [(437.5±49.3) mm3]. There was no statistically significant difference in the superior and inferior muscle volume ratio of the lateral rectus in three groups (all P>0.05), while the ratio in group B was more dispersive. Conclusions: The pulley location changes of four extraocular rectus muscles of patients with concomitant exotropia and small-angle vertical deviation in primary gaze are not significant, but the medial rectus volume in patients who had concomitant exotropia with vertical deviation or not is significantly smaller. The dispersive superior and inferior muscle volume ratio of the horizontal rectus muscles may be related to the small angle of vertical deviation in clinical examinations. (Chin J Ophthalmol, 2021, 57: 223-227).

[Clinical observation of anterior tucking of the superior oblique tendon for correction of excyclotropia in adults].

Objective: To investigate the clinical effect of anterior 1/3 superior oblique tendon tucking in acquired symptomatic excyclotropia adults. Methods: Retrospective case series. Seven patients (7 eyes) with acquired symptomatic excyclotropia who underwent an anterior 1/3 superior oblique tendon tuck procedure in Tianjin Eye Hospital from January 2019 to December 2019 were included. There were 5 male patients and 2 female patients, with an average age of (49±12) years old. All the patients had a history of a closed head injury. There was torsional diplopia in primary position, and eye movement examination showed paralysis of the superior oblique muscle in the affected eye, without obvious hyperactivity of the inferior oblique muscle. The anterior 1/3 tendon of the superior oblique muscle was tucked during surgery according to the relaxation of the superior oblique tendon in the forced duction test. The paired-sample nonparametric rank sum test was used to analyze the preoperative and postoperative (at 1 day after surgery and the last follow-up) excyclotropia angle. Results: The mean tuck amount was (7.7±1.8) mm (range, 6.0 to 10.0 mm). During operation, patients complained that excyclotropia improved markedly. The excyclotropia angle with the double Maddox rod test improved significantly from preoperative 10° (8°, 15°) to 2° (0°, 3°) at 1 day (Z=-2.379; P<0.05) and 2° (2°, 5°) at the last follow-up (Z=-2.375; P<0.05). The follow-up period was (112+38) days. All patients had no complaints of excyclotropia at the last follow-up. Conclusions: The anterior 1/3 superior oblique tendon tucking can effectively improve clinical symptoms in the primary position in adults with acquired excyclotropia and diplopia. The short-term postoperative results seem to be stable, without significant regression. (Chin J Ophthalmol, 2021, 57: 685-688).

The investigation of hepatitis A virus and hepatitis E virus co-infection in humans and animals in China.

The aim of this study was to investigate the prevalence of co-infection of hepatitis A and hepatitis E virus (HAV/HEV) in patients with acute hepatitis as well as in different animal species. A total of 46 serum samples from patients diagnosed as hepatitis A or hepatitis E and 675 fecal samples of 11 animal species were collected. The IgM class antibodies to HEV and HAV, respectively, were detected by enzyme-linked immunosorbent assay. HEV and HAV RNAs were extracted from serum and fecal samples for the nested reverse transcription polymerase chain reaction. At least 10.9% (5/46) of the patients were co-infected with both HAV and HEV. Fifteen percent (18/120) of rabbit fecal samples and 17.5% (7/40) of swine fecal samples were positive for HEV RNA, but only 1% (2/200) of ferret fecal samples were positive for HAV RNA. Our study showed that co-infection with both HAV and HEV in patients and animals is infrequent. At least in our study, we showed that ferrets may represent the potential HAV hosts. Keywords: hepatitis A virus; hepatitis E virus; co-infection; zoonosis; prevalence.

[Study of association between drinking water and gastric cancer of the residents in Sheyang county Jiangsu Province: a case-control study].

A total of 189 new cases of gastric cancer in Sheyang County from 2014 to 2018 were selected as the case group, and 189 other people without gastric cancer were matched according to age and gender as the control group. A case-control study was conducted on the relationship between drinking water and gastric cancer. After adjusting BMI, family annual income, dietary taste, monthly pickle consumption, monthly chili consumption, monthly soy product consumption, whether experiencing misfortune, whether suffering from superficial gastritis, whether having family history of gastric cancer, the results of multivariate logistic regression showed that compared with those who had no sources of pollution at the end of drinking water 10 years ago and who mainly consumed boiled water, those who had sources of pollution at the end of drinking water 10 years ago and who only drank raw water had a higher risk of stomach cancer ï¼»OR (95%CI) were 2.20 (1.13-4.29), 6.12 (1.25-29.93)ï¼½; Compared with drinking water source from tap water, the risk of stomach cancer of those who drink clean water is lower ï¼»OR (95%CI): 0.55 (0.35-0.85)ï¼½; And those who drink more water every day have a lower risk of stomach cancer ï¼»OR (95%CI): 0.67 (0.48-0.92)ï¼½.

[Paying attention to the application of imaging examination in strabismus].

There are many pathogenic factors of strabismus. In addition to the changes of alignment and ocular movement, there may be abnormal pathways and development of extraocular muscles, abnormalities of orbital and intraorbital connective tissue, paralysis of cranial nerves (oculomotor nerve, trochlear nerve, and abductor nerve), and nuclear and supranuclear lesions, accompanied by other cerebral dysplasia sometimes. In recent years, advances in imaging technology and its application in the professional field of strabismus have made it possible to clearly observe the eye, orbital, intracranial, and innervation changes, which is helpful to clarify the etiology of strabismus and extraocular muscle-related diseases, and to provide a basis for the diagnosis and treatment of strabismus. Strabismus specialists should learn and pay attention to the application of imaging examination, so as to achieve in-depth understanding and accurate treatment. (Chin J Ophthalmol, 2020, 56: 166-170).

[A study of superior oblique muscle changes in superior oblique palsy using magnetic resonance imaging].

Objective: To observe the magnetic resonance imaging(MRI) changes of superior oblique muscle and to study the relationship between changes and clinical signs in superior oblique muscle palsy. Methods: Cross-sectional study. Data was collected from January 2014 to January 2016 in Tianjin Eye Hospital. Twenty-three(30 eyes) patients who were diagnosed with superior oblique palsy included 15 patients with congenital superior oblique palsy [9 males and 6 females aged (32±13) years (range, 12-53 years)] and 8 cases with acquired superior oblique palsy [3 males and 5 females aged (36±15) years(range, 17-62 years)]. Twenty normal volunteers [11 males and 9 females aged (35±13) years (range, 15-60 years)] were also observed. Coronal MRI was used to detect superior oblique muscle morphological changes, as well as the maximum cross-sectional area and volume changes. The relationship between the morphological changes and vertical deviation and cyclotorsion in the primary gaze was analyzed. Rank sum test, t-test and Person correlation analysis were used for statistical analysis. Results: Two morphological changes were obtained using MRI in superior oblique muscle palsy, including round (19 eyes) and oval changes (11 eyes). The maximum cross-sectional area in eyes with the palsied superior oblique muscle [round, (10.38±1.76) mm(2); oval, (11.16±2.02) mm(2)] was significantly smaller than fellow eyes [(14.16±1.88) mm(2); Z=6.208, 5.178, both P<0.001] and eyes with normal superior oblique muscle [(15.40±1.71) mm(2); Z=8.215, 6.330, both P<0.001], and the volume changes [round, (104.92±13.36) mm(3); oval, (110.43±16.11) mm(3)] were also significantly different from fellow eyes [(254.57±20.15) mm(3); Z=7.511, 5.396, both P<0.001] and eyes with normal superior oblique muscle [(258.04±16.36) mm(3); Z=10.040, 6.936, both P<0.001]. There was no significant difference in vertical deviation between round and oval superior oblique muscle palsies (P>0.05). The cyclotorsion effect of the round change in superior oblique muscle palsy was significantly less than that of the oval change (5.47°±1.05° vs. 7.36°±0.97°, t=3.083, P=0.005). The correlation of the volume changes with vertical deviation angle in the primary gaze was not significantly different (round and oval, both P<0.05), but there was a correlation between the morphological changes and cyclotorsion strabismus (r=0.631, P=0.004; r=0.801, P=0.003). Conclusions: In the patients with superior oblique palsy, MRI scans shows that the maximum cross-sectional area decreased and the volume was smaller, which indicated superior oblique muscle atrophy. Deformation of superior oblique muscle do not significantly affect the vertical deviation, but is in correlation with cyclodeviation. (Chin J Ophthalmol, 2019, 55:20-24).

[Advances in research of synergistic divergence].

Synergistic divergence is a rare condition characterized by complete absence of adduction that is associated with simultaneous abduction of the affected eye on attempted adduction. This causes the affected eye to move further into abduction on gaze to the normal side and results in extreme divergence of both eyes. It is sometimes referred to as exotropic Duane syndrome with synergistic divergence (type 4 Duane syndrome) or congenital fibrosis syndrome with synergistic divergence. Diseases combined with synergistic divergence fall within the category of congenital cranial dysinnervation disorders (CCDDs). The ocular associations reported with synergistic divergence are uncommon and include Horner syndrome, ocular albinism, foveal hypoplasia, Goldenhar syndrome and pupillary abnormalities. MRI and electro-oculographic study suggested that this is the result of CCDDs. Various surgical techniques have been tried in individual cases including large recession of the lateral rectus muscle, lateral rectus muscle extirpation, large resection of the medial rectus (MR) muscle, weakening procedures of the oblique muscles, combination of lateral rectus orbital wall fixation with MR resection, but further investigations with large-scale samples are needed. Recent research advances in the definition, etiology, and treatment of synergistic divergence are reviewed in this article. (Chin J Ophthalmol, 2019, 55:63-67).