[Advancements in research on immune responses associated with adeno-associated virus vector-mediated ocular gene therapy].

Adeno-associated virus (AAV) vectors have been widely employed in gene therapy for ocular and systemic diseases. However, clinical trial outcomes have indicated that gene therapy may trigger severe adverse events associated with immune-inflammatory reactions, thereby impacting the safety and efficacy of gene therapy. The immune-inflammatory reaction induced after gene therapy in the eye is referred to as gene therapy-associated uveitis, which has become a major obstacle limiting the long-term and effective use of ocular gene therapy. This review comprehensively explores four aspects: the immune response mechanisms of gene therapy, ocular manifestations of associated uveitis, factors influencing immune inflammation, and preventive and therapeutic strategies. The aim is to provide insights for the development of safer and more effective ocular gene therapy.

[Advances in gene therapy of ocular surface and corneal diseases].

With the continual advancement of gene editing technology, gene therapy has been increasingly explored as a potential treatment option for both hereditary and acquired diseases. Due to its unique physiological and anatomical characteristics, the eye has emerged as an optimal target for gene therapy. In fact, ophthalmology was among the first clinical fields to obtain approval for in vivo gene therapy. Despite the widespread development of gene therapy targeting ocular surface and corneal diseases in recent years, a systematic review of these projects is still lacking. Thus, this review aims to comprehensively summarize the research progress and clinical application of gene therapy for ocular surface and corneal diseases, providing valuable guidance for future research and clinical translation.

[A special on epidemic prevention and control: analysis on expression of 2019-nCoV related ACE2 and TMPRSS2 in eye tissues].

This article was published ahead of print on the official website of Chinese Journal of Ophthalmolog on Apirl 22,2020. Objective: Angiotensin converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2) are the key proteins for 2019-nCoV entry into host cells. To evaluate the potential infection risk of 2019-nCoV on ocular surface, we compared ACE2 and TMPRSS2 expression among different eye tissues. Methods: Experimental study. Thirty mice were assigned to male, female, aged, diabetic and non-diabetic groups, with 6 mice in each group. Real-time PCR was performed to quantify ACE2 and TMPRSS2 gene expression in conjunctiva, cornea, lacrimal gland, iris, lens, retina, lung, heart, kidney, and liver from male mice. Immunohistochemistry staining was applied to visualize the distribution of the two proteins in different mice tissues, and in human corneal and conjunctival sections. Published transcriptome datasets were extracted to generate the expression comparasion of ACE2 and TMPRSS2 between human conjunctival and corneal tissues, and results were analyzed using Mann-Whitney U test. Female mice, aged mice, STZ-induced diabetic mice, diabetic group control mice were also subjected to ACE2 expression analysis. Results were analyzed using Student's t-test. Results: The expression of ACE2 and TMPRSS2 genes were the highest in conjunctiva among all the six mice eye tissues explored. The expression of these two genes in conjunctiva were lower than that in kidney and lung. ACE2 and TMPRSS2 shared similar expression pattern with the staining concentrated in corneal epithelium, conjunctival epithelium and lacrimal gland serous cells. The expression levels of ACE2 showed gender difference. Female mice had lower ACE2 in conjunctiva and cornea than male mice, with the expression levels being only 43% (t=3.269, P=0.031) and 63% (t=4.080, P=0.015) of that in the male conjunctiva and cornea, respectively. Diabetic mice expressed more ACE2 in conjunctiva (1.21-fold, P>0.05) and lacrimal gland (1.10-fold, P>0.05) compared with the control group. No significant difference on ACE2 expression was found between the aged and young adult mice. The expression level of human conjunctiva ACE2 and TMPRSS2 were significantly higher than that in the cornea (P=0.007), with 5.74-fold and 12.84-fold higher in the conjunctiva than in the corneal epithelium cells, which resembled the situation in mice. Conclusion: The observation of high-level ACE2 and TMPRSS2 expression in conjunctiva among the 6 eye tissues examined suggests that conjunctiva serves as an infection target tissue of 2019-nCoV. (Chin J Ophthalmol, 2020, 56:438-446).

[The correlations of single photon emission computed tomography joints scan and bone metabolic markers in active rheumatoid arthritis].

Objective: To explore the correlation between quantitative value of joint bone scan by single photon emission computed tomography(SPECT) and serum bone metabolic markers in patients with active rheumatoid arthritis(RA). Method: Clinical data of 60 newly diagnosed RA patients were retrospectively collected in Department of Rheumatology and Immunology from May 2013 to December 2014, including 28 cases with medical history less than 6 months and 32 from 6 months to 2 years. Serum C-terminal telopeptide of type Ⅰ collgen(CTX-Ⅰ)and N-terminal propeptide of type Ⅰ collagen(PINP)were tested by chemiluminesence. SPECT whole body bone and target joint scan before treatment was done. Thirty-nine healthy subjects as control group received ultrasound, electrocardiogram, X-ray, and whole body bone imaging examination. Quantitative values of joint imaging were calculated for the statistical analysis. Result: Demographic data between RA group and control group were comparable (P>0.05), including sample, sex, age and BMI. The joint SPECT value, CTX-Ⅰ and PINP levels were all significantly higher than those of control group (P<0.01), which were 6.48±1.98 versus 3.73±1.16; (0.66±0.37) mg/L versus (0.58±0.21) mg/L; (46.35±28.15) mg/L versus (30.47±13.75) mg/L respectively. Joint SPECT values had positive correlations with serum CTX-Ⅰ levels in all RA patients, as well as PINP in patients with disease duration 6mon-2years. And the according correlation coefficients were 0.513, 0.495, 0.402(P<0.05). But SPECT value had no correlation with CTX-Ⅰ (P=0.081) in patients with disease duration less than 6 mon.The correlation coefficient was 0.336. Conclusion: SPECT imaging quantitative values were positively correlated with serum bone metabolic parameters. Thus SPECT imaging alone or combined with bone markers are helpful in diagnosing active RA.

[China faces a challenge of breast cancer prevention and control].

The incidence and mortality of breast cancer is in an increasing trend. In contrast to the global breast cancer situation, the prevention and control is challenging in China. Some suggestions are presented to the project of breast cancer prevention and control in China. Combining the global screening experiences with the epidemiological features of Chinese female breast cancer, aims to improve the population screening and early detection rate. Standardizing clinical diagnosis and treatment practice, aims to increase the efficacy and decrease the mortality. Intervening lifestyle and dietary behaviors, and intends to reduce risk exposure and incidence. Building national breast cancer registry provides preventive strategies. Great efforts should be made to carry out large sample multicenter clinical trails and translational research on the prevention and cotrol of breast cancer coordiated by health care service and science and technology administrations. Breast cancer prevention and control has a long way to go in China.

Clinicopathological features of invasive lobular carcinoma of the breast: A nationwide multicenter study in China.

OBJECTIVE: To analyze the clinicopathological features of invasive lobular carcinoma (ILC) and compare them with invasive ductal carcinoma (IDC), hoping to find the fact of ILC in China and assist the decision makers with proper individualized treatment. MATERIALS AND METHODS: A nationwide multicenter retrospective study was performed. A total of 4211 primary breast cancer cases were randomly selected from 1999 to 2008 in seven regions of China. ILC cases were compared with IDC by clinicopathological features and molecular subtypes. RESULTS: A total of 135 (3.2%) ILC and 3471 (82.4%) IDC cases were included for analysis. The age, tumor size, menopausal state, family history, nodal status, and stage of ILC were similar to that of IDC. ILC was more likely to be positive for estrogen receptor (65.5% vs. 57.7%) and progesterone receptor (64.7% vs. 58.5%), and less likely to overexpress human epidermal growth factor receptor-2 (17.3% vs. 23.6%). Even though, these differences are not significant, the proportion of luminal A type of ILC is significantly larger than that of IDC (54.8% vs. 42.7%; P < 0.05). CONCLUSION: ILC has a larger proportion of luminal A type compared with IDC. Larger sample size study for better known of molecular subtypes of ILC is needed in future to individualize the treatment decision.

Age interactions in breast cancer: an analysis of a 10-year multicentre study in China.

OBJECTIVES: The effects of age at diagnosis on the clinical characteristics of breast cancer and trends over time were investigated in Chinese women. METHODS: Data from 4211 women with pathologically confirmed primary breast cancer collected between 1999 and 2008 for a multicentre retrospective study were analysed according to age at diagnosis. RESULTS: Age at diagnosis ranged from 21 to 86 years, with a mean of 48.7 years, and was shown to be significantly related to tumour size, lymph node status, hormone receptor status and human growth factor receptor-2 status, but not to pathological type or tumour, node, metastasis stage. The age-corrected proportion of patients aged 50-64 years at diagnosis increased significantly between 1999 and 2008. There was a significant difference in the age-corrected distribution of age at diagnosis in China compared with Western countries. CONCLUSIONS: Age at diagnosis is related to the clinical and pathological characteristics of breast cancer. The age at diagnosis in China increased over the decade from 1999 to 2008, but is still lower than in Western countries.

Tumor formation suppressed in gammadeltaT knock-out mice.

Tumor formation was examined in mice in which the beta-chain gene of alphabetaT was knocked out (alphabetaT-KO mice) or the delta-chain gene of gammadeltaT was knocked out (gammadeltaT-KO mice). Development of Hepa 1-6 cell hepatoma was observed in six of six alphabetaT-KO mice, in four of six wild-type mice, and in only one of six gammadeltaT-KO mice. These results imply that gammadeltaT cells play a role in suppression of killer cell activity in tumor-bearing mice.

[Tuberculosis of the breast misdiagnosed as breast cancer].

The authors report 15 patients with tuberculosis of the breast initially misdiagnosed as breast cancers. Criteria of differentiation of breast tuberculosis were: incidence (Tbc: cancer = 1: 245), lacking in constant site of involvement, possible concomitant involvement of other organs, eg. lung tuberculosis, youth of the patient, multi-para and history of breast feeding, in isolated cases, co-existence of tuberculosis and cancer is not impossible. The authors stress meticulous care in evaluating the history, symptoms, signs and supplementary examinations. Needle biopsy and pathology are indicated.

[Paget's disease of the nipple].

Fifty-five female patients with Paget's disease of the nipple treated in our Hospital from 1958 to 1987 are reported. It comprised 1.1% of all the breast carcinomas. The lesions was on the left side in 27 and on the right side in 28. The average age was 48 years. The primary lesion was in breast ducts and then invaded the nipple, areola superficially and deeper breast tissue. Dermal manifestation of Paget's disease is easily confused with chronic dermopathy. In this series, four patients (7.2%) did not have the typical symptoms so pathologic or cytologic examination was relied upon for correct diagnosis. Thirty-one patients were treated by radical mastectomy giving a 3-year disease-free rate of 70.9%. It seems that radical mastectomy is more superior to the other surgical procedures. The 3-year recurrent rate was 38% for patients with Paget's disease of the nipple coexisting with breast carcinoma, but no recurrence was found in patients with simple Paget's disease of the nipple. The 3-year survival rate was 46.4% in patients with axillary lymph node metastasis, 85.2% in patients without, 54.3% in patients with palpable masses in the breast and 85.0% in patients without. Paget's disease of the nipple coexisting with breast carcinoma, axillary lymph node metastasis, palpable breast masses has poor prognosis.

[Flow cytometer (FCM) in biological characteristics of nasopharyngeal carcinoma xenografts in nude mice].

Tumor tissue from a patient with nasopharyngeal carcinoma was transplanted to nude mice (BALB/c) and had successfully been maintained through ten passages. The nude mice tumor and the primary human tumor were assayed by FCM for the DNA content in addition to conventional pathological examination, chromosome analysis and EBV assay. The tumor incidence in the different passages showed a marked change ranging from 25% to 81% with a mean value of 52% which tended to increase, however. The doubling time of six tumors in the ninth passage showed no great change 6-12 weeks after transplantation with a mean about 4.3 days. But at week 12, there was a significant difference between each tumor volume, ranging from 438 to 1,998 mm3. By FCM, it was found that the DNA index remained constant in both the primary and nude mice tumors. Among the nude mice tumors in different passages, the distribution of various phase cells in cell cycle was similar to that of the primary tumor. In conclusion, the use of FCM to assay the cellular DNA content in nude mice tumor is rapid and sensitive. It is helpful, for the nude mice tumor, in identifying stability of the biological characteristics and in studying of the mechanism of chemotherapy and radiotherapy in the future.