[The pathological characteristics and prognostic analysis of medullary thyroid microcarcinoma].

Objectives: To analyze the clinical characteristics and prognosis of medullary thyroid microcarcinoma (MTMC). Methods: A case series studies. The clinical data of patients with medullary thyroid carcinoma (MTC) diagnosed by postoperative pathology and with complete follow-up data who were initially treated in Tianjin Medical University Cancer Hospital from January 2013 to December 2019 were retrospectively analyzed. There were a total of 170 cases, including 70 males and 100 females, aged (49.7±12.3) years old. Among them, there were 61 patients with MTMC. They were divided into group A (with a maximum tumor idameter of ≤0.5 cm, n=13) and group B (with a maximum tumor diameter >0.5~≤1.0 cm, n=48) based on whether the maximum diameter of the tumor was >0.5 cm. Analysis was conducted on their pathological results and prognosis. Results: Among the MTC, MTMC accounted for 26.4% (61/231) with 26 males and 35 females aged Mï¼»Q1，Q3ï¼½51.0 (41.0, 59.0) years. Among the MTMC patients, 57.4% (35/61) were in stage Ⅰ, 16.4% (10/61) were in stage Ⅲ, and 26.2% (16/61) were in stage Ⅳ. For MTMC with a maximum diameter of≤0.5 cm and a maximum diameter of >0.5-≤1.0 cm, there was no statistically significant difference between the two groups in terms of gender, age, mixed cancer, invasion of glandular lobes, multifocal, central lymph node metastasis, lateral neck lymph node metastasis rate and other pathological characteristics(both P>0.05). In terms of prognosis, the recurrence free survival time of MTMC patients was 83.1 (68.0, 97.0) months. Among them, structural tumor recurrence occurred in 5 patients (8.2%) after surgery, and 1 patient (1.6%) died. The expected 5-year and 10-year survival rates were 93.4% and 89.0%, respectively. There was no statistically significant difference in recurrence free survival time among MTMC patients, MTC patients with a maximum diameter of >1.0-≤2.0 cm, and MTC patients with a maximum diameter of >2.0 cm (all P>0.05). Conclusion: MTMC has strong invasiveness, and although the prognosis of most MTMCs is relatively good, the risk of long-term recurrence and death is still high.

[Cohort study on the association between hyperopia reserve and myopia incidence in primary school students: the Anyang Childhood Eye Study].

Objective: To analyze the longitudinal association between hyperopia reserve and the cumulative incidence of myopia in grade 1 primary school students. Methods: Cohort study. This study included 2 628 grade 1 primary school students (2 628 eyes) who without myopic at baseline from the Anyang Childhood Eye Study. There were 1 515 male and 1 113 female, aged(7.16±0.40) years. Every year, cycloplegic autorefraction was performed with 1% cyclopentolate eye drops to obtain data of hyperopia reserve. Students with different ranges of hyperopia reserve at baseline were analyzed. Axial length, anterior chamber depth, corneal curvature, lens thickness, and other parameters were obtained by ocular biometrics and compared by the independent sample t test. Qualitative data were described by frequency and percentage, and comparison between groups was performed by the Chi-square test or exact probability method. Linear regression was used to analyze the association between baseline hyperopia reserve and spherical equivalent at 5 years. Results: The average hyperopia reserve was (+1.09±0.78) diopters (D) in grade 1 non-myopic children. Axial length, anterior chamber depth, corneal radius of curvature, and lens thickness were (22.66±0.72), (2.88±0.24), (7.80±0.25) and (3.62±0.19) mm, respectively. The cumulative incidence of myopia among non-myopic grade 1 primary school students was 8.5%, 21.5%, 35.6%, 47.6% and 64.1% at 1, 2, 3, 4 and 5 years, respectively. The incidence of myopia in girls was significantly higher than that in boys at 3, 4 and 5 years. The 5-year cumulative incidence of myopia was 4.6%, 26.3%, 52.3%, 78.6%, 92.6% and 94.3%, respectively, corresponding to students with baseline hyperopia reserve of >+2.00 D,+1.50 D to +2.00 D,+1.00 D to +1.50 D,+0.50 D to +1.00 D, 0.00 D to +0.50 D and -0.50 D to 0.00 D, and the difference was statistically significant (χ²=490.59, P<0.001). The regression equation between baseline hyperopia reserve and 5-year spherical equivalent was as follows: 5-year spherical equivalent=-3.135+1.692·baseline hyperopia reserve (R2=0.454, P<0.001). Conclusions: The lower the hyperopia reserve, the higher the incidence of myopia. Monitoring children's hyperopia reserve and early protection to reduce its consumption and timely detection of children at high risk of myopia are of great significance to prevent the occurrence and development of myopia.(This article was published ahead of print on the Online-First Publishing Platform for Excellent Scientific Researches of Chinese Medical Association Publishing House on March 15, 2022).

[The key points and difficulties in prevention of myopia in Chinese children and adolescents].

Myopia has emerged as a public health problem with its increasing prevalence in children and adolescents in China. The Chinese government has begun to take action to address this issue in recent years. In 2018, the Implementation Plan of the Myopia Prevention and Control for Children and Adolescents was issued by the Ministry of Education and other seven ministries and commissions. The plan emphasizes the myopia prevention and management will be a powerful national strategy to a major crisis of children's health in China. Based on the current situation and characteristics of myopia in children and adolescents in China, this article analyzes the key points and difficulties of related work, so as to provide scientific ideas and references for prevention and control of myopia in China. (Chin J Ophthalmol, 2021, 57:241-244).

[Emphasizing the standardized use of cycloplegics in the epidemiological studies of myopia].

The prevalence of myopia in China is extraordinarily high, and much attention has been paid to the epidemiological studies related to myopia. Epidemiological investigations can be used to understand the incidence and prevalence of myopia, its epidemiological characteristics and the related risk factors. At present, there are many articlespublished in China on epidemiological surveys of myopia. However, the criteria for cycloplegic regimes are not uniform, the age limit is not definite, and cycloplegics are even not used in some researches. Lack of or insufficient cycloplegia is associated with overestimation of the prevalence of myopia and underestimation of hyperopia and leads to inaccurate assessment of risk factors. In this article, we propose standardized methods for cycloplegia in the epidemiological investigations of myopia in China by reviewing different types of cycloplegic regimes commonly used and the effects on different age groups. This will help to obtain the accurate incidence and prevalence of myopia, promote the interconnection and increase comparabilityof research data, improve the accuracy of assessing related risk factors and provide scientific evidence for the prevention and control of myopia. (Chin J Ophthalmol, 2019, 55: 561-564).

[An investigation on professional performance of optometric refraction in spectacles stores in Anyang city of Henan Province].

Objective: To investigate the methods of optometric refraction adopted for adolescents in spectacles stores in Anyang city of Henan Province and the professional performance of optometric refraction. Methods: Cross-sectional study. Maps and yellow pages were used to collect the information of 131 spectacles stores in Anyang city. A questionnaire was used to investigate spectacles stores that had optometry equipment and can provide refraction prescription and spectacles in this city. The questionnaire covered (1) the process of optometric refraction, including whether cycloplegic refraction was conducted for adolescents and children if it was their first-time optometry and the type of cycloplegics,and (2) the opticians' knowledge on optometric refraction for adolescents and children, such as necessity of cycloplegic refraction for adolescents and children and age cut-offs. According to whether they used a comprehensive refractometer, the optometry methods were divided into conventional optometry and medical optometry. Results: Of 131 spectacles stores in Anyang city, 127 were enrolled. A total of 127 questionnaires were distributed and returned with an effective rate of 100%. Conventional optometric refraction was performed in 53 stores (41.73%), and medical optometric refraction was performed in 74 stores (58.27%). Cycloplegic refraction was conducted in only 4 spectacles stores (3.15%) for adolescents and children upon their first-time optometry. The fogging method of refraction was adopted in 31 stores (24.41%), while optometric refraction was directly conducted in 92 stores (72.44%) without controlling accommodation. As for the use of cycloplegia at initial optometric refraction of children, cycloplegia was objected to in 4 stores,and thought to be no need in 28 stores including 6 stores in which the fogging method was used to replace cycloplegia. In 68 stores, cycloplegia was performed if wanted, or children could go to a hospital for it. In 12 stores, the use of cycloplegics was determined by children's vision and diopters. In 5 stores, children were suggested to go to a hospital for cycloplegic refraction. Cycloplegic refraction was required in only 4 stores. As to the age cut-offs of cycloplegic refraction, 6 years old, 12 years old, and 18 years old were considered as the boundary in 7 stores, 33 stores, and 9 stores, respectively.In 11 stores, age was only considered for amblyopia and hyperopia, and in 67 stores, it was not realized. Conclusions: Cycloplegic refraction was found to be conducted for adolescents and children in only 3% of the spectacles stores in Anyang city. Moreover, most of the spectacles store opticians did not support to use cycloplegia before optometric refraction for adolescents and children and lacked knowledge on the age cut-offs of cycloplegic refraction.Standardized training of cycloplegic refraction should be further strengthened. (Chin J Ophthalmol, 2019, 55: 576-581).

[Efficacy and safety of pegylated interferon α-2b injection (Y shape, 40 kD) in treatment of patients with genotype 1/6 chronic hepatitis C].

Objective: To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control. Methods: A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed. Results: A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group. Conclusion: In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.

[Correlations of serum TgAb and TPOAb and clinicopathological features of PTC in children and adolescents].

Objective: To analyze the correlations between serum thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) and clinicopathological features in children and adolescents with papillary thyroid carcinoma (PTC). Methods: A retrospective analysis was conduced on the clinicopathological data of children and adolescents (age≤21 years old) with PTC admitted to Tianjin Medical University Cancer Hospital from 2011 to 2019, and then, we used χ2 test or Fisher's exact probability test to compare the differences in clinicopathological characteristics between groups with different TgAb and TPOAb status and multivariate logistic regression model analysis to evaluate independent predictors of cervical lymph node metastasis. Results: A total of 304 patients, including 89 males and 215 females, aged 5-21 years (median age 19 years), were enrolled in this study. The comparison between groups with different TgAb and TPOAb status showed that there were significant differences in gender, preoperative thyroglobulin (Tg) level, primary tumor location, number of primary tumors and maximum tumor diameter (all P<0.05), which suggested that TgAb+group (n=81) and TPOAb+group (n=84) had relatively better primary tumor characteristics. Patitents with TgAb+and TPOAb+were more common in females and their preoperative Tg level was mostly within the normal range, and there were significant differences in primary tumor location, number of primary tumors and maximum tumor diameter between TgAb+and TgAb-(223 cases) groups (all P<0.05). There was significant difference in the maximum tumor diameter between TPOAb+and TPOAb-(220 cases) groups (P<0.05). Analysis of risk factors for cervical lymph node metastasis showed that independent risk factors for central lymph node metastasis were maximum tumor diameter>2 cm (OR=2.84, 95%CI: 1.59-5.07, P<0.001) and extra-thyroid extension (OR=0.32, 95%CI: 0.17-0.60, P<0.001), and independent risk factors for lateral neck lymph node metastasis included age≤14 years old (OR=0.34, 95%CI: 0.18-0.67, P=0.002), preoperative Tg+(OR=2.16, 95%CI: 1.10-4.24, P=0.026) and maximum tumor diameter>2 cm (OR=3.99, 95%CI: 2.33-6.82, P<0.001). Conclusion: It is recommended to test routinely serum TgAb and TPOAb before surgery in children and adolescents with PTC. Preoperative Tg+, age≤14 years, maximum tumor diameter>2 cm, and extra-thyroid extension are risk factors for cervical lymph node metastasis.

Influence of Treg cells and HBV genotype on sustained response and drug resistance in the treatment with nucleoside drugs.

We aimed to investigate the influence of regulatory T cells including CD4+CD25+, CD8+CD28- and hepatitis B virus (HBV) genotype on sustained virological response and tolerance of nucleoside drugs. One hundred and thirty-seven patients were enrolled. Lamivudine was administered to 84 patients. Entecavir was administered to the other 53 patients. Before treatment, biochemical tests, HBV DNA load, HBV serum level, HBV genotype, PB CD3+, CD4+, CD8+, CD4+CD25+/CD3+, and CD8+CD28-/CD3+ frequencies were measured. Based on HBV DNA loads after 4 weeks of therapy, patients were divided into response group and suboptimal response group. The lamivudine group received treatment continuously, and then patients were categorized into non-resistance group and resistance group. Compared with the suboptimal response and resistance groups for lamivudine, CD4+CD25+/CD3+ levels were higher in the response and non-resistance groups (t=4.372, P=0.046; t=7.262, P=0.017). In the non-resistance group, CD8+CD28-/CD3+ frequency was lower than in the resistance group (t=5.527, P=0.037). Virus load and hepatitis B E antigen (HBeAg)-positive rate were significantly lower than in the response and resistance group (t=2.164, P=0.038; X2=4.239, P=0.040; t=2.015, P=0.044; X2=16.2, P=0.000). Incidence of drug resistance was high in patients with virogene type C. For the virological response to entecavir, CD8+CD28-/CD3+ level was significantly lower than that of the suboptimal response group (t=6.283, P=0.036). Response and suboptimal response groups were compared in CD3+, CD4+, CD8+, CD4+CD25+/CD3+ and virus genotype, and differences were not statistically significant (P>0.05). Baseline regulatory T cells including CD4+CD25+/CD3+ and CD8+CD28-/CD3+ frequencies have a relationship with the incidence of rapid virological response and the resistance to nucleoside drugs. Patients with HBV genotype C receiving lamivudine more often underwent drug resistance. Antiviral efficacy and the resistance to lamivudine were closely correlated with baseline factors; the same cannot be found for entecavir.

Suitability of bone marrow from HIV-1-infected donors for retrovirus-mediated gene transfer.

Bone marrow samples from 21 human immunodeficiency virus type 1 (HIV-1)-infected subjects were evaluated for their suitability for retrovirus-mediated gene transduction with anti-HIV-1 genes. The percentages of CD34+ cells that could be isolated from the mononuclear fraction of bone marrow samples were determined. Fifteen of the 21 marrow samples had normal percentages of CD34+ cells isolated by immunomagnetic methods. All seven donors with CD4 counts > 100/mm3 had normal percentages of CD34+ cells; of 14 patients with low CD4 cell counts (< 100/mm3), 5 had reduced and 9 had normal percentages of CD34+ cells. Samples of the marrow were plated in a methylcellulose colony-forming unit (CFU) assay to determine the clonogenic capacity of the progenitor cells. Overall, the marrow samples from HIV-infected donors showed a 44% reduction in CFU derived from the mononuclear cell fraction and a 75% reduction in CFU derived from the isolated CD34+ cell fraction, when compared to marrow samples from uninfected donors. Isolated CD3+ cells were transduced with retroviral vectors containing various anti-HIV-1 genes to determine their susceptibility to gene transfer. Transduction of the clonogenic CD34+ cells by retroviral vectors did not differ among marrow samples from 13 HIV-1+ donors and 9 uninfected donors. Long-term bone marrow cultures established from the transduced CD34+ cells demonstrated equivalent survival of clonogenic progenitor cells from both HIV-1-infected and uninfected marrows. Toxicity from expression of the anti-HIV-1 genes was not observed; the percentages of clonogenic progenitor cells that survived in cultures transduced by vectors carrying anti-HIV-1 genes were similar to those transduced by the control LN vectors. Stromal cells cultured from marrow samples from HIV-1-infected donors showed similar growth kinetics, hematopoietic support function, and enhancement of retrovirus-mediated transduction of CD34+ cells as seen with stromal cells cultured from uninfected marrow donors. Semi-quantitative polymerase chain reaction (PCR) was performed before and after ex vivo transduction to determine the frequency of HIV-1-containing cells in the CD34+ cell preparations. Although HIV-1+ cells were present at low levels in the mononuclear cell fractions of some of the marrow samples, the CD34+ cell preparation from only one marrow sample contained detectable HIV-1 positive cells (< 1 positive cell/100,000 by PCR) prior to transduction. None of the CD34+ cell preparations contained detectable HIV-1 after transduction. These studies demonstrate that HIV-1-infected patients are candidates for retrovirus-mediated transduction of anti-HIV-1 genes in bone marrow gene therapy clinical trials.