[Observation on the efficacy of different targets low-frequency repetitive transcranial magnetic stimulation for the treatment of tremor-dominant subtypes of Parkinson's disease].

Objective: To analyze the efficacy of different targets low-frequency repetitive transcranial magnetic stimulation (rTMS) for the treatment of tremor Parkinson's disease(PD). Method: A total of 82 patients with primary PD who were admitted to the Department of Neurology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 1, 2020 to March 31, 2021 were prospectively collected. According to the clinical characteristics of major movement disorders, 82 patients with tremor type (TD) were selected to enroll.The patients were randomly divided into 3 groups at a 1∶1∶1 ratio according to the randomized coding sequence of the trial: the primary motor cortex (M1) group with 26 cases, the cerebellum group with 26 cases and the dual-site (M1, cerebellum) group with 30 cases. All patients were treated with 1 Hz low-frequency stimulation of the corresponding target once a day for 5 days a week for 2 weeks, a total of 10 times; The dosage remained unchanged during the treatment for all groups. Before and after 2 weeks' treatment, the patients were assessed with the Unified PD Rating Scale (UPDRS) and PD Quality of Life Questionnaire-39 (PDQ-39) without medication. Cortical excitability, namely transcranial magnetic stimulation motor evoked potential (TMS-MEP), [including resting motor threshold (rMT) and active motor threshold (aMT) examinations], timed up and go (TUG) and electromyographic tremor were conducted. Result: There were 82 patients, 39 males and 43 females, with an average age of (67±8) years. Before the treatment, there was no statistically significant difference in the evaluation indicators among the three groups (all P>0.05). After the treatment, the differences of the UPDRS-Ⅲ score [(38.9±2.5) vs (29.2±3.6) ], UPDRS tremor score [(23.7±2.1) vs (14.6±3.1) ], TUG time [(44.8±3.1) s vs (33.7±4.1) s], tremor amplitude [(480±126) µV vs (276±94) µV], PDQ-39 score [(51±13) vs (45±13) ], rMT [(36±17)% vs (43±13)%], and aMT [(26±16)% vs (31±12)%] were statistically significant (all P<0.01) from those before the treatment. There was no statistical difference in the above factors between the M1 group and cerebellum group (all P>0.05). There was no statistically significant difference in tremor peak frequency among the three groups before and after the treatment (all P>0.05). Conclusions: Dual-site low-frequency rTMS can improve PD tremor, while M1 or cerebellar low-frequency rTMS does not significantly improve PD tremor. Its mechanism may be to improve PD tremor symptoms by regulating cortical excitability.

[The clinical efficacy of the stratification medical treatment based on the risk estimation of motor complications in Parkinson's disease].

Objectives: To evaluate the clinical efficacy of the stratification medical treatment based on the motor complications risk estimation in improving the quality of life, motor symptoms and delaying the motor complications in Parkinson's patients. Methods: Outpatients and inpatients from Xinhua Hospital, Shanghai Jiao Tong University, were recruited between November 2019 and June 2020. The participants were all clinically diagnosed with PD and treated with anti-PD medications, but had no history of motor complications, with the 8-item Parkinson's disease questionnaire summary index (PDQ-8 SI)>18.59. At baseline, the demographic characteristics, PD medical history, levodopa dosage (LD) and levodopa equivalent dosage (LED) were collected, and the evaluation of PDQ-8, Unified Parkinson's disease rating scale (UPDRS)-Ⅱ and Ⅲ, Hoehn and Yahr (H&Y) grade, Hamilton anxiety scale-14 (HAMA-14), Hamilton depression scale-24 (HAMD-24), mini-mental state examination (MMSE), Pittsburgh sleep quality index (PSQI), and Epworth sleepiness scale (ESS) tools was accomplished in all participants. Meanwhile, a Parkinson's disease risk estimation scale for motor complications was used to assess patients' risk of motor complications, and thus the medication was stratified in PD patients accordingly. During the 6-month and 12-month follow-ups, the evaluation of the above-mentioned parameters was repeated in all participants. At the 3-month and 9-month follow-ups, the information of anti-PD medications, the occurrence of motor complications (motor fluctuations and dyskinesia) and adverse drug reactions were recorded, and PDQ-8 was also evaluated. Results: Two hundred and fifty-one patients completed the 1-year follow-up, with 135 males and 116 females. At baseline, the median age of the patients was 66 (60, 71) years and the median PDQ-8 SI was 31.2 (21.9, 40.6). Additionally, 15.9% (40/251) of the patients were at high risk of motor fluctuation, and 7.2% (18/251) were at high risk of dyskinesia. There were significant differences in the age of onset, disease duration, PD treatment duration, the scores of UPDRS-Ⅱ and Ⅲ, H&Y Grade, and PDQ-8 SI among PD patients of different risk groups (all P<0.05). In the 12th month, the median of PDQ-8 SI, Δ PDQ-8 SI and Δ UPDRS-Ⅲ was 12.5 (9.4, 18.8), -15.6 (-21.9, -9.4) and -9(-16, -4), respectively, which was statistically different from that of baseline (all P<0.05). The change of UPDRS-Ⅱ scores in the group with high risk of motor fluctuation was statistically different from that in the groups with low and moderate risk (P<0.05). The changes of PSQI score, LD and LED in the group with high risk of dyskinesia was statistically different from those in the groups with low and moderate risk (all P<0.05). During the follow-up, the incidence of motor fluctuation and dyskinesia was 9.56% (24/251) and 5.97% (15/251), respectively. Conclusion: The stratification medical treatment might have a positive intervention effect on promoting a better quality of life, improving motor symptoms and delaying motor complications in PD patients.

[Associations between 24-hour urinary sodium excretion and all-cause mortality in adults living in north China].

Objective: To investigate the associations between 24-hour urinary sodium excretion (24hUNaE) and all-cause mortality in adult Northern Chinese population. Methods: Data from this study were derived from the prospective urban and rural epidemiology (PURE) study in north China. Baseline information of all participants were obtained by face to face interview through trained research staffs based on questionnaires, and morning fasting urine samples of participants were collected to estimate 24hUNaE and 24-hour potassium excretion (24hUKE). Multivariable frailty Cox regression models were used to explore the association between 24hUNaE (<3.00, 3.00-3.99, 4.00-4.99, 5.00-5.99 and ≥6 g/d) and all-cause death. Results: A total of 27 310 participants were included in this study. The mean 24hUNaE was (5.84±1.73) g/d. After a median follow-up of 8.8 years, 1 024 participants died (3.7%), including 390 cardiovascular related deaths and 591 non-cardiovascular related deaths. The cause of death of the remaining patients could not be determined. Using 24hUNaE level of 4.00-4.99 g/d as the reference group, after fully adjustment, 24hUNaE ≥6.00 g/d was associated with an increased risk of all-cause death (HR=1.24, 95%CI: 1.02-1.49) and cardiovascular related death (HR=1.39, 95%CI: 1.02-1.88). 24hUNaE<3.00 g/d was associated with increased risk of all-cause mortality (HR=1.38, 95%CI: 0.96-1.99). There was no significant association between 24hUNaE and non-cardiovascular related death. Furthermore, using the combination of 24hUNaE 4.00-4.99 g/d and 24hUKE≥2.11 g/d as the reference group, the highest risk occurred in participants with the combination of low sodium (<3.00 g/d) and low potassium (<2.11 g/d). Conclusion: 24hUNaE equal or higher than 6 g/d or lower than 3 g/d is associated with increased risk of all-cause mortality and cardiovascular related death in Northern Chinese population. Besides, moderate sodium intake in combination with increased potassium intake might reduce the risk of all-cause death.

[Pay attention to the mental disorders related dry eye].

The number of patients suffering from both dry eye and mental disorders (especially anxiety and depression) has risen rapidly in ophthalmic clinics. However, the mental disorders related dry eye has not received enough attention. At present, it lacks related information of basic data, and there is no standard for the clinical diagnosis and treatment. To this end, this article aims to determine the role of mental factors in the pathogenesis of dry eye, to strengthen the relevant basic and clinical research, to standardize its clinical diagnosis and treatment, and thus to promote the prevention and treatment of the mental disorder related dry eye in China.

[Association between meibomian gland dysfunction and body mass index in Chinese adults].

Objective: To evaluate the association of meibomian gland dysfunction (MGD) and body mass index (BMI) in Chinese adults. Methods: A total of 2 419 patients were retrospectively recruited between May and October 2013 from 33 ocular surface disease clinic in China. There were 780 males (32.2%) and 1 639 females (67.8%), aged 18-89 (46±16) years. BMI value of each patient was respectively calculated, and the patients were divided into underweight, normal weight, overweight and obesity groups accordingly. Meibomian gland-related examinations were performed in right eyes. Results: The number of the patients in four groups were 196, 1 556, 567 and 100, respectively. Compared with normal weight group, the rates of moderate to severe MGD (59.1%, 71.0% vs 49.9%) in overweight group and obesity group were higher, and the differences were statistically significant (both P<0.05). The scores of change in eyelid margin, meibomian gland dropout and meibum expressibility were significantly higher in overweight group and obesity group, compared with normal weight group (all P<0.05). Additionally, after stratified by age, all the above-mentioned three scores of obese patients were significantly higher than those of non-obese patients in young adult group. Multivariate logistic regression analysis showed that moderate to severe MGD was correlated with overweight (OR=2.19, 95%CI: 1.06-4.50, P=0.033) and obesity (OR=3.70, 95%CI: 2.57-5.04, P=0.008). Conclusion: Moderate to severe MGD significantly correlates with high BMI in Chinese adults.

[Effect of binocular accommodation and vergence function examinations and interventions on subjective discomfort of dry eye].

Objective: To investigate the accommodation and vergence (AV) function of patients with mild to moderate refractory dry eye symptoms, and determine the impact of relevant interventions on subjective symptoms. Methods: A total of 103 patients with dry eye disease (DED) in Zhongshan Ophthalmic Center between December 2017 and June 2019 were included. After 3-month conventional treatment, the patients entered the treatment-responsive group if ocular surface disease index (OSDI) decreased ≥12.5, and others were recruited into the refractory symptoms group. Binocular AV function, OSDI, tear break-up time (TBUT), Schirmer's test (ST) and fluorescein staining (FL) were determined in all the patients. Corrective therapy on the AV dysfunction was added in the refractory symptoms group besides the conventional therapy. The above-mentioned indexes were reexamined 8 weeks later. The incidence of AV dysfunction was compared between the refractory symptoms group and the treatment-responsive group. Moreover, the differences of OSDI and tear film stability were compared before and after the corrective therapy in the refractory symptoms group. Results: Sixty of 103 DED patients were classified into the refractory symptoms group [mean age: (27±6) years; 18 males and 25 females] and 43 into the treatment-responsive group [mean age: (30±6) years; 32 males and 28 females]. The incidence of AV dysfunction in the refractory symptom group (100%) was higher than that of the treatment responsive group (72.1%) (P<0.001). Forty patients with refractory symptoms accomplished the 8-week corrective therapy, and the OSDI score was significant improved (23.4±16.0 vs 40.6±15.7, P<0.001). However, further changes in ST, TBUT and FL were not detected in these patients (all P>0.05). Conclusions: There is a high prevalence of AV dysfunction in patients with refractory symptomatic DED. The corrective therapy on AV may improve the subjective symptoms in these patients.

[A multicenter, randomized, double-masked, placebo-controlled trial of compound wild chrysanthemum eye masks for mild and moderate dry eye].

Objective: To investigate the clinical efficacy and safety of compound wild chrysanthemum eye masks for mild and moderate dry eye. Methods: In this double-masked, multicenter, placebo-controlled, randomized trial, middle-aged and elderly patients with mild and moderate dry eye were enrolled from six hospitals (Xiamen Eye Center of Xiamen University, China-Japan Friendship Hospital, Peking Union Medical College Hospital, Wangjing Hospital of China Academy of Chinese Medical Sciences, Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine and Hebei Eye Hospital). The patients were assigned to the compound wild chrysanthemum eye mask group and the eye mask simulator group based on the random number table. Subjective symptoms of dry eye, visual acuity, break-up time (BUT), Schirmer Ⅰ test, and corneal fluorescent staining were evaluated in all patients before treatment and at 1 and 2 weeks after treatment. All adverse reactions during the treatment and follow-up were recorded. Results: A total of 120 patients were enrolled. Among them, 112 subjects were included for statistical analyses after the exclusion of 8 subjects who were lost for follow-up or had an adverse event, with an age of (54.26±7.44) years. All the indicators were equally comparable between the two groups. Before treatment and at 1 and 2 weeks after treatment, the median (lower quartile, upper quartile) of total score of questionnaires in the eye mask group was 14.50 (10.00, 19.00), 9.00 (5.00, 14.00) and 7.00 (4.00, 10.00), respectively, and that in the control group was 14.00 (9.00, 22.50), 12.00 (6.00, 20.00) and 10.00 (3.50, 17.00), respectively. The score decreased significantly in both groups after 1 week (t=9.1604, S=398.00; P<0.01) and 2 weeks (S=681.00, 575.50; P<0.05) of treatment. The total score of questionnaires in the eye mask group was significantly lower than that in the control group (Z=3.27, 2.81; P<0.05) after treatment. After 1 week of treatment, the average BUT of the eye mask group was (5.71±2.31) s, which was significantly longer than that before treatment (5.06±2.00) s (S =208.50, P<0.05). But there was no significant difference in the control group (S=150.00, P>0.05). After 2 weeks of treatment, there was statistically significant difference in BUT between the two groups (S=407.00, t=3.07; P<0.01). After 1 week of the treatment, the amount of tear secretion in the eye mask group [(6.88±4.78) mm] was significantly larger than that before treatment (S=196.50, P<0.05), while the control group [(6.80±5.85) mm] showed no significant difference (S=55.00, P<0.05). After 2 weeks of the treatment, the amount increased significantly to (7.43±4.86) mm and (7.29±4.56) mm, respectively, in both groups (t=-3.29, -2.26; P<0.05). The difference in the average BUT, Schirmer Ⅰ test result and corneal fluorescent staining between both groups was not statistically significant at each time point. Five mild adverse events occurred, including 2 adverse events (2 times, 3.51%) in the eye mask group and 3 adverse events (4 times, 5.36%) in the control group. Conclusions: Compound wild chrysanthemum eye masks can effectively improve the symptoms and physical signs of mild and moderate dry eye and can be used as an auxiliary treatment. (Chin J Ophthalmol, 2021, 57: 601-607).

[Efficacy of a recombinant bovine basic fibroblast growth factor gel for the treatment of moderate dry eye: a multicenter randomized double-blind parallel controlled clinical trial].

Objective: To compare the clinical efficacy of a recombinant bovine basic fibroblast growth factor (rb-bFGF) gel and a gel matrix in the treatment of moderate dry eye. Methods: It was a prospective random double-blind controlled study. One hundred patients diagnosed as moderate dry eye in Eye Institute and Affiliated Xiamen Eye Center of Xiamen University, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Beijing Tongren Hospital, Capital Medical University, Eye & ENT Hospital of Fudan University and Zhongshan Ophthalmic Center from August 2015 to April 2019 were divided into two groups: experimental group and control group. Two groups of patients were allocated to receive either a rb-bFGF gel or a gel matrix 4 times per day for 4 weeks. Subjective symptoms, break-up time of the tear film (BUT), Schirmer Ⅰ test (SⅠt) and corneal fluorescein sodium staining were assessed at baseline, 2 and 4 weeks after treatment. Bulbar impression cytology was evaluated at baseline and 4 weeks after treatment. Irritation of the rb-bFGF gel and the gel matrix was estimated after treatment. T test, Wilcoxon signed-rank test or Mann-Whitney U test was used for quantitative data, and Chi-square test was used for enumerative data. Results: Eighty-four subjects were included for statistical analyses after the exclusion of 16 subjects who were lost for followup, with an age of 43±14 years. There were 42 cases in the experimental group and the control group, respectively. There was no statistically significant difference between the two groups in demographic baseline characteristics before treatment (P>0.05). The total score of subjective symptoms was 7.17±3.60 and 5.95±3.25 at 2 and 4 weeks after therapy in the experimental group, which were lower than 9.48±3.88 before treatment (t=6.226, 6.563; both P<0.05); in the control group, it was 7.01±3.25 and 6.32±3.85 at 2 and 4 weeks after treatment, with a significant reduction in comparison with that before treatment (9.15±3.58; t=4.693, 4.726; both P<0.05). The median (lower quartile, upper quartile) BUT was 4.00 (2.40, 5.00) s and 4.64 (3.00, 5.00) s at 2 and 4 weeks after therapy in the experimental group, which were longer than 3.72 (2.00, 4.39) s before treatment (Z=-2.485, -3.152; both P<0.05). The BUT was 4.41 (2.79, 5.12) s at 2 weeks after therapy in the control group, which was of no statistical difference compared with 3.89 (2.09, 4.25) s before treatment (Z=-1.953, P>0.05). The BUT was 5.21 (3.00, 5.02) s at 4 weeks after therapy in the control group, which was longer than that before treatment (Z=-2.485, P<0.05). The SⅠt score was 7.31 (3.75, 10.00) mm and 8.50 (4.00, 11.00) mm at 2 and 4 weeks after therapy in the experimental group, which were significantly higher than 6.69 (2.00, 8.13) mm before treatment (Z=-2.031, -2.236; both P<0.05); in the control group, it was 6.82 (2.00, 8.25) mm and 6.86 (3.00, 9.25) mm at 2 and 4 weeks after therapy, which were not significantly increased compared with 6.50 (2.00, 7.75) mm before treatment (Z=-0.179, -1.161; both P>0.05). The corneal fluorescein sodium staining points were 5.00 (2.00, 5.00) and 3.71 (0.00, 5.00) at 2 and 4 weeks after therapy in the experimental group, which were significantly lower than 7.10 (5.00, 7.00) before treatment (t=-2.895, -4.639; both P<0.05); those in the control group were 5.52 (0.00, 7.00) and 6.19 (0.75, 6.25) at 2 and 4 weeks after treatment, with a significant reduction in comparison with 8.90 (5.00, 10.50) before treatment (t=-2.776, -1.991; both P<0.05). The differences in the average total score of subjective symptoms, BUT, SIt, and corneal fluorescein sodium staining points between both groups were not statistically significant at each time point. The impression cytology grade was decreased from 1.72 (1.00, 2.00) before treatment to 0.94 (0.00, 2.00) at 4 weeks after therapy in the experimental group (Z=-2.803, P<0.05). The staining grade of conjunctival imprinted cells in the control group was 1.42 (1.00, 2.00) at 4 weeks, which showed no statistical significance compared with 1.56 (1.00, 2.00) before treatment (Z=1.195, P>0.05). The impression cytology grade was significantly reduced in the experimental group compared with the control group at 4 weeks after treatment (Z=-3.308, P<0.05). The number of goblet cells was 10.90 (5.00, 20.00) at 4 weeks after therapy in the experimental group, which was significantly higher than 6.30 (5.00, 8.00) before treatment (Z=-2.383, P<0.05); in the control group, it was 8.36 (4.00, 12.00) at 4 weeks after treatment, with no significant increase in comparison with that before treatment [7.55 (5.00, 11.00)] (Z=-0.095, P>0.05). The number of goblet cells was not significantly increased in the experimental group compared with the control group at 4 weeks after treatment (Z=-1.162, P>0.05). Most patients indicated that the drug was non-irritating, and no patient had intolerable irritation affecting daily lives at 4 weeks after therapy; there was no difference between the two groups (Z=-0.290, P>0.05). Conclusions: Both the rb-bFGF gel and the gel matrix can effectively improve the symptoms and signs of moderate dry eye. However, compared with the gel matrix, the rb-bFGF gel shows obvious advantages in promoting conjunctival epithelial cell repair and increasing the number of goblet cells. (Chin J Ophthalmol, 2021, 57: 930-938).

[A multicenter randomized prospective study of concurrent chemoradiation with 60 Gy versus 50 Gy for inoperable esophageal squamous cell carcinoma].

Objective: To determine whether 60 Gy is superior to standard 50 Gy for definitive concurrent chemoradiation(CCRT) in esophageal squamous cell carcinoma (ESCC) using modern radiation technology in a phase Ⅲ prospective randomized trial. Methods: From April 2013 to May 2017, 331 patients from 22 hospitals who were pathologically confirmed with stage ⅢA-ⅣA ESCC were randomized to 60 Gy or 50 Gy with random number table. Total of 305 patients were analyzed, including 152 in 60 Gy group and 153 in 50 Gy group. The median age was 63 years, 242(79.3%) males and 63(20.7%) females. The median length of primary tumor was 5.6 cm. The clinical characteristics between two groups were comparable. All patients were delivered 2 Gy per fraction, 5 fractions per week. Concurrent weekly chemotherapy with docetaxel (25 mg/m(2)) and cisplatin (25 mg/m(2)) and 2 cycles consolidation chemotherapy with docetaxel (70 mg/m(2)) and cisplatin (25 mg/m(2), d1-3) were administrated. The primary endpoint was local/regional progression-free survival (LRPFS). The data were compared with Pearson chi-square test or Fisher's exact test. Results: At a median follow-up of 27.3 months, the disease progression rate was 37.5% (57/152), 43.8% (67/153) in the high and standard-dose group, respectively (χ(2)=1.251, P=0.263). The 1, 2, 3-year LRPFS rate was 75.4%, 56.8%, 52.1% and 74.2%, 58.4%, 50.1%, respectively (HR: 0.95, 95%CI: 0.69-1.31, P=0.761). The 1, 2, 3-year overall survival rate was 84.1%, 64.8%, 54.1% and 85.4%, 62.9%, 54.0%, respectively (HR: 0.98, 95%CI: 0.71-1.38, P=0.927). The 1, 2, 3-year progression-free survival rate was 70.8%, 54.2%, 48.5% and 65.5%, 51.9%, 45.1%, respectively (HR: 0.93, 95%CI: 0.68-1.26, P=0.621). The incidence rates in toxicities between the two groups were similar except for higher rate of severe pneumonitis in high dose group (χ(2)=11.596, P=0.021). Conclusions: The efficacy in disease control is similar between 60 Gy and 50 Gy using modern radiation technology concurrent with chemotherapy for ESCC. The 50 Gy should be recommended as the regular radiation dose with CCRT for ESCC.

[Preliminary study of the antibody level in confirmed patients with COVID-19 after discharge].

Objective: To analyze the antibody levels and dynamic changes in patients infected with 2019-novel coronavirus(2019-nCoV). Methods: The average age of 72 corona virus disease 2019 (COVID-19) patients was (45.53±16.74)years(median age:47 year), including (44.88±17.09) years(median age:46 year) for 38 males and (46.32±16.52)years (median age:46 year) for 34 females in Loudi City, Hunan Province. There is no significant difference in genders between the severe and mild groups (χ²=0.916, P>0.05). There is a significant difference in the age between the severe and mild groups (F=3.315, P<0.05). The blood samples of 72 discharged patients were collected and the consistence of IgM and IgG antibodies were detected by chemiluminescence method. SPSS25.0 was used for gender, age, case type and antibody analysis of variance, χ2 test and other analysis. Results: The average time of the serum samples collection of 72 patients was (34.89±9.02)days (median time: 34 days) from onset of COVID-19, and (14.53±8.35) days (median time: 14 days) from discharge. The positive rate of IgM or IgG was 97.22% (70/72), and the positive rate of IgM and IgG was 48.61% (35/72) and 97.22% (70/72) respectively. Serum COVID-19 antibodies were detected in 72 patients from 1st to 40th days after discharge. The average concentration of IgM in 1-7 days, 8-14 days, 15-21 days, 22-28 days, above 29 days were 21.91(7.07-52.84)AU/ml, 14.16(6.19-32.88)AU/ml, 11.36(6.65-42.15)AU/ml, 8.15(3.66-30.12)AU/ml, 2.98(0.46-6.37)AU/ml. There was no significant difference in the time of IgM antibody concentration (H= 8.439, P>0.05). The average concentrations of IgG in 1-7 days, 8-14 days, 15-21 days, 22-28 days, 29 days and above were 169.90 (92.06-190.91) AU/ml, 163.89 (91.19-208.02) AU/ml, 173.31 (95.06-191.28) AU/ml, 122.84 (103.19-188.34) AU/ml, 101.98 (43.75-175.30) AU/ml, respectively, (H=2.232, P>0.05). The IgM becomes negative after the 3rd week of discharge and decreases rapidly with time. The IgG concentration higher than IgM during the same period, and keep at high level without any change, and decrease in the fourth week. Among them, 5 cases developed "re-infection" within 1-3 weeks after discharge, and the rate of "re-infection" was 6.94% (5/72 cases). Conclusions: After the COVID-19 patients are discharged from the hospital, the level of antibodies produced varies greatly among individuals, but the overall changes in antibodies have a certain pattern. It is recommended to strengthen the antibody monitoring during hospitalization and after discharge from the hospital to reduce the "re-infection" rate and potential risk of infection.

[Paying attention to the expert consensus on dry eye to standardize and promote the clinical diagnosis and treatment of dry eye].

Dry eye is the most common chronic eye disease other than refractive errors. The expert consensus on dry eye has guiding significance in standardizing as well as improving the clinical diagnosis and treatment of dry eye in our country. The development of dry eye consensus needs to be rigorous, while its operability should be the key in clinics. In the routine clinical work, doctors should pay full attention to the guidelines of dry eye consensus, follow the advice in reason, correctly apply new technologies and new methods, and avoid improper applications. On this basis, we also encourage to continue innovations and explorations, which will eventually improve the clinical and research levels of dry eye in China. (Chin J Ophthalmol, 2020, 56:726-729).

[The value and application prospect of cyclosporine A in the treatment of dry eye].

Dry eye is the most common ocular surface disease, the core pathogenesis of which is ocular surface inflammation. Anti-inflammation is one of the important clinical treatments of dry eye. Since the definitely immunosuppressive effect, topical ophthalmic cyclosporine A (CsA) has been used in dry eye for many years. A large number of studies have been published in recent years, including its therapeutic effects, indications and applications. This article will introduce the mechanism of ophthalmic CsA, summarize its clinical treatment effects in dry eyes of different countries, different causes, and different severity. Meanwhile we will analyze the pros and cons and the applied prospects of ophthalmic CsA with various forms, and generalize the indications, treatment suggestions and safety of CsA used in dry eye, in order to provide references for the clinical applications. (Chin J Ophthalmol, 2020, 56:787-795).

Vasoactive intestinal peptide is required in the maintenance of immune regulatory competency of immune regulatory monocytes.

Dysfunction of the immune regulatory system plays an important role in the pathogenesis of rheumatoid arthritis (RA). Vasoactive intestinal peptide (VIP) has multiple bioactivities. This study aims to investigate the role of VIP in the maintenance of the immune regulatory capacity of monocytes (Mos). Human peripheral blood samples were collected from RA patients and healthy control (HC) subjects. Mos and CD14+ CD71- CD73+ CD25+ regulatory Mos (RegMos) were isolated from the blood samples and characterized by flow cytometry. A rat RA model was developed to test the role of VIP in the maintenance of the immune regulatory function of Mos. The results showed that RegMos of HC subjects had immune suppressive functions. RegMos of RA patients expressed less interleukin (IL)-10 and showed an incompetent immune regulatory capacity. Serum levels of VIP were lower in RA patients, which were positively correlated with the expression of IL-10 in RegMos. In-vitro experiments showed that the IL-10 mRNA decayed spontaneously in RegMos, which could be prevented by the presence of VIP in the culture. VIP suppressed the effects of tristetraprolin (TTP) on inducing IL-10 mRNA decay in RegMos. Administration of VIP inhibited experimental RA in rats through restoring the IL-10 expression in RegMos. RegMos have immune suppressive functions. VIP is required in maintaining IL-10 expression in RegMos. The data suggest that VIP has translational potential in the treatment of immune disorders such as RA.

[Application of radial artery in arterialized coronary artery bypass grafting in Chinese patients].

Objective: To summarize the application of radial artery (RA) as the second arterial graft in coronary artery bypass grafting (CABG). Methods: From January 1, 2015 to June 11, 2019, the clinical data of all patients undergoing CABG in TEDA International Cardiovascular Hospital was retrospectively reviewed. The patients who underwent RA grafting were included. The application of RA, internal mammary artery (IMA) and the saphenous vein, their target vessels, and the operative results were analyzed. Results: A total of 2 901 patients underwent CABG. Of those, 208 patients (7.2%) had RA grafting, with 197 males and 11 females. The average age was (53±8) years old and the average grafts per patient was 3.79. The target vessel for RA was first obtuse marginal (OM, 102 cases), first diagonal (50 cases), right coronary artery (RCA) or posterior descending artery (PDA) (40 cases), intermediate (22 cases), respectively. Among those, 172 were single distal anastomosis with the proximal end anastomosed to the ascending aorta (168 cases), saphenous vein (SV) graft (3 cases) and IMA (1 case). Seventy-two patients accept sequential grafting with the proximal to the ascending aorta (58 cases), SV graft (13 cases) and IMA (1 case). The left IMA was mainly anastomosed to left descending artery (LAD) (188 cases) and diagonal (10 cases). The target vessels for SV were remaining coronary arteries when the IMA and RA were used. The operative time was (5.0±1.5) h. The hospital stay was (17.4±6.4) d. There were 6 cases undergoing exploratory thoracotomy for bleeding (5 cases) or hemodynamic instability due to ventricular arrhythmia (1 case). There was no death. All patients were successfully discharged. Conclusions: Use of the RA and IMA with additional SV for CABG exhibits good results in the Chinese patients. Currently available clinical protocols are effective and safe.

[Focusing on the functional dry eye].

Dry eye is one of the most common eye diseases characterized by disturbance of tear film homeostasis and a series of ocular discomforts. Discrepancy of ocular subjective symptoms and objective signs, especially unexplained severe symptoms without visible signs has been a long-time confusion for ophthalmologists. Functional disorder is a medical condition that impairs normal functioning of bodily processes due to autonomic nervous dysfunction caused by cerebral cortical dysfunction, but at the exterior, there is no appearance of abnormality. Clinical manifestations are the disease symptoms with a lack of exact physical signs and examination results to confirm the diagnosis. According to the definition and characteristics of functional disorder, we put forward the concept of functional dry eye. We assume that those patients with dry eye symptoms but without detectable signs could be classified into such a functional dry eye subtype. The possible mechanism, clinical manifestations, and treatment strategies are further discussed. (Chin J Ophthalmol, 2019, 55: 885-890).

[Recent studies on the signaling pathways implicated myopia].

Myopia has emerged as one of the major health issues in China given its increasingly high prevalence. It is generally accepted that myopia is the result of a complex interaction of environmental exposures and genetic predisposition. Many studies have indicated that abnormal visual stimulation regulates retinal neurotransmitters and growth factors to release resulting in scleral remodeling and axial elongation through signaling pathway transduction. It has been reported that the signaling pathways play important roles in the elongation of axial length and development of myopia. In this study, we reviewed several important signaling pathways implicated myopia.(Chin J Ophthalmol, 2019, 55:148-152).

Vitamin D receptor interacts with NLRP3 to restrict the allergic response.

Vitamin D receptor (VDR) mediates various biochemical activities between the cytoplasm and the nucleus in the cell. The nucleotide-binding, oligomerization domain (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) protein is involved in the T helper type 2 (Th2) response. This study tests a hypothesis that VDR interacts with NLRP3 to restrict the Th2-biased response. In this study, VDR-/- mice and WT (WT) mice were used. Th2 cell differentiation between VDR-/- mice and WT mice was observed. We observed that CD4+ T cell activation was higher in VDR-/- mice. The VDR-/-CD4+ T cells were prone to Th2 polarization. VDR-/- mice produced more immunoglobulin (Ig)E. VDR bound NLRP3 to prevent Th2 differentiation by restricting IL4 gene transcription. Th2 biased inflammation spontaneously developed in the intestine of VDR-/- mice. In conclusion, VDR binds NLRP3 to restrict IL4 gene transcription and prevent biased Th2 polarization.

Targeting histone-acetyltransferase Tat-interactive protein 60 inhibits intestinal allergy.

BACKGROUND: The overproduction of IgE plays a critical role in the pathogenesis of allergy; the mechanism is unclear. Histone-acetyltransferase (HAT) activities are required in gene transcription of a large number of molecules in the immune system of the body. OBJECTIVES: This study tests a hypothesis that HAT Tat-interactive protein 60 (Tip60) plays an important role in the initiation of IgE-mediated allergy. METHODS: The effects of Tip60 on regulating IgE expression were assessed with B cells. An intestinal allergy mouse model was developed to assess the role of Tip60 in the induction of IgE-mediated allergic inflammation. RESULTS: High levels of Tip60 were observed in the peripheral B cells of patients with FA. Tat-interactive protein 60 (Tip60) was required in the expression of IgE and IgG1 in B cells by inducing the chromatin remolding at the gene locus, in which histone acetylation, signal transducer and activator of transcription 6 (STAT6), and nuclear factor-κB at the locus of Iε promoter were markedly increased. Blocking Tip60 significantly attenuated the allergic inflammation in the mouse intestinal mucosa. CONCLUSIONS: Tat-interactive protein 60 (Tip60) plays an important role in the induction of IgE in B cells. Blocking Tip60 inhibits the allergic inflammation in the intestine, suggesting Tip60 inhibitor may be a potential anti-allergy drug.

Long-term effects: Galectin-1 and specific immunotherapy for allergic responses in the intestine.

BACKGROUND AND AIMS: Mast cell activation interferes with the effects of allergen-specific immunotherapy (SIT). Galectin-1 (Gal-1) is capable of regulating immune cells' functions. This study tests the hypothesis that administration of Gal-1 promotes and prolongs the efficacy of SIT via suppressing mast cell activation. METHODS: An intestinal allergy mouse model was developed. The coadministration of SIT and Gal-1 on suppression of the allergic responses, prevention of mast cell activation, and generation of antigen-specific regulatory T cells (Treg) in the intestine was observed in sensitized mice. RESULTS: The coadministration of Gal-1 and SIT markedly suppressed the allergic responses in the mouse intestine vs the use of either SIT alone or Gal-1 alone. The Gal-1 binds to the IgE/FcɛRI complexes on the surface of mast cells to prevent mast cell activation during SIT. Gal-1 promoted the SIT-generated allergen-specific Tregs in the intestine of sensitized mice. Coadministration of Gal-1 and SIT significantly enhanced the efficacy of immunotherapy in suppressing allergic responses in the intestine, which lasted for at least for 12 months. CONCLUSIONS: Long-term effects of specific immunotherapy on intestinal allergy can be achieved with Gal-1/SIT therapy by inhibiting mast cell activation and facilitating Treg development.

Diagnosis and treatment of distal limb microcirculatory disturbance caused by steroid injection.

Corticosteroid is commonly used for the clinical treatment of pain. It is safe, reliable and a simple procedure with other advantages. However, a possible potential catastrophic complication of corticosteroid injections in distal limbs (e.g., the wrist) is acute radial artery ischemia due to the injection into the radial artery. This may result from spasm attributed to the steroids. While the complication of corticosteroids in the wrist is rare, ischemia of the hand caused by corticosteroid injections in radial artery has been reported in several articles. We treated five patients with microcirculation disturbance of distal limb caused by corticosteroid treatment. Here, we report the two different treatment strategies adopted according to the severity of the disease which achieved good therapeutic effects.