[Health economic evaluation of telemedicine diabetic retinopathy examination using a non-mydriatic fundus camera in China].

Objective: To perform a health economic evaluation of telemedicine diabetic retinopathy (DR) examination with a non-mydriatic fundus camera in China and to investigate the optimal examination interval. Methods: Based on 18 peer-reviewed articles related to epidemiology, clinical trial, and health economic evaluation of DR, surveys from 9 ophthalmologists in 3 tertiary hospitals in China, price lists for medical services in each province, and the negotiated price in 2021, a Markov model was conducted to evaluate the cost utility of telemedicine eye examination for diabetes mellitus patients aged 45 and older from the health system perspective. Separate analyses were performed for no examination and for examination intervals of every 1 to 5 years to predict the lifetime health gain, including cumulative days of blindness, cumulative life years, and quality-adjusted life years (QALYs), and costs for unilateral and bilateral direct medication with a 3.5% discount rate. Results: The cumulative days of blindness in the absence of a DR screening were 2 375.00 days, and ranged from 701.00 to 738.00 days for five different DR screening interval programs. The cumulative life years for no screening and five DR screening programs ranged from 27.120 34 to 28.005 00 years, with QALYs ranging from 9.502 96 to 9.875 02. The direct medication costs in the absence of a DR screening program were 72 785.00 yuan for both unilateral and bilateral scenarios. For the five DR screening intervals, the direct medication costs ranged from 52 065.00 to 52 408.00 yuan for unilateral and 79 100.00 to 79 603.00 yuan for bilateral. Comparing the incremental cost-effectiveness ratios between the DR screening intervals and no screening, the 1-to 5-year intervals were dominant in the unilateral scenario (between -56 368.54 and -55 523.75 yuan/QALY). In the bilateral scenario, the ratios ranged from 17 469.07 to 18 325.15 yuan/QALY. Using a willingness-to-pay threshold equal to the per capita GDP (80 976 yuan/QALY), the 1-year DR screening interval had an 85.9% probability of being cost-effective and a 55.2% probability of being dominant in the unilateral scenario. In the bilateral scenario, the 2-year interval held a 61.4% probability of being cost-effective. Conclusions: Analyses on the remote fundus consultation in diabetic patients and health economics based on the Markov model indicate that telemedicine DR examination through a non-mydriatic fundus camera can be effectively employed for diabetes mellitus patients in China. DR examination every two years is recommended for general diabetic patients, and DR examination every year may be chosen in developed areas.

[Eosinophilic solid and cystic renal cell carcinoma with TSC2 gene mutations in children].

Objective: To study clinical pathological characteristics, immunohistochemical, molecular genetical changes and prognosis in pediatric eosinophilic solid and cystic renal cell carcinoma (ESC RCC) with TSC2 gene mutations. Methods: The tissue samples were collected from two pediatric ESC RCC patients between 2017 and 2018. The tissues were subjected to histological examination and immunohistochemistry using EnVision system. The TFE3, TFEB gene rearrangements were tested using FISH and molecular genetic study. The paraffin sections were used for DNA extraction, PCR amplification and NGS sequencing. Results: The two patients with ESC RCC were both male, aged at 9 years and 8 months, and 13 years, respectively. The tumors were from the right kidney, 5 cm and 7 cm in size, respectively, with solid and cystic changes in cross section, and grey-reddish or grey-whitish fish meat appearance. Microscopic observation revealed the tumors had fibrous capsules, which were infiltrated by the tumor cells. The tumor cells were diffusely distributed, round-shaped, or polygon-shaped, and had voluminous cytoplasm, eosinophilic cytoplasm, various sizes of vacuoles and clear cell-like appearance. There were papillary structures in some areas, with visible fiber septa. The nuclei were round and vesicular, with multi-nucleated cells and megakaryocytes. The mitoses were not seen. A few cystic structures were visible in different sizes, and capsule walls were covered with a single layer of spike-like tumor cells. Thick-walled blood vessels were seen in the stroma, with focal lymphocytic infiltration, eosinophilic necrosis, calcifications and cholesterol crystals. Immunohistochemistry of the tumor cells was positive for PAX8 (diffuse), CK20 (focal), CKpan (focal), CK10 (1 focal, 1 diffuse), INI1, vimentin, CD68, and Ki-67 (5%~10%); the tumor cells were negative for HMB45, S-100, Melan A, p53, desmin, TFE3, CK7, CK19, EMA, CD56, CgA, Syn, CD30, CD117, WT1 and SMA. Molecular genetic study showed that TFE3 and TFEB gene rearrangements were not detected by FISH. NGS sequencing showed TSC2 p.Lys574Ter (0.198) was found in patient one and TSC2 p.Arg406Ter (0.355) in patient two. Conclusions: ESC RCC in children is a rare disease, and can be misdiagnosed easily. It has unique pathological characteristics, and immunohistochemical, molecular and genetic changes. The prognosis is relatively good.

[Results of sentinel surveillance on men who have sex with men in Jilin province between 2010 and 2015].

Objective: To explore the HIV epidemic and related factors among MSM in Jilin province. Methods: During the implementation of sentinel surveillance program from 2010 to 2015, continuous cross-sectional studies were conducted to monitor the awareness of AIDS, sexual behavior, HIV and syphilis positive rates, with the sample size no less than 400 in each surveillance site. Results: From 2010 to 2015, a total of 7 823 MSM were involved in this study. The overall HIV prevalence among MSM was 5.4% (42/7 823), with an increasing trend during 2010 and 2015 (Trend test χ(2)=110.023, P<0.001). The rates of awareness on AIDS were higher than 90.0%. The proportion of consistent condom use was 27.0% (2 112/7 823) in the last 6 months, and significant differences were found in these years (χ(2)=234.038, P<0.001). Results from multivariate logistic regression analysis showed that the HIV infection related risk factors among MSM in Jilin province would include: residency from other provinces (aOR=1.797, 95%CI: 1.185-2.726), recruitment through internet (aOR=1.717, 95%CI: 1.332-2.215), diagnosed of having sexually transmitted diseases in the previous year (aOR=1.893, 95%CI: 1.356-2.643) and positive testing on syphilis (aOR=4.309, 95%CI: 3.097-5.995). And consistent condom uses in the last 6 months (aOR=0.387, 95%CI: 0.143-0.557), tested HIV in the last year (aOR=0.632, 95%CI: 0.375-0.891) were preventive factors. Conclusions: HIV prevalence was increasing among MSM in Jilin province, but both the proportion of consistent condom use and the former HIV testing rate were at a low level. Aggressive measurement including consistent condom use and periodical HIV testing among MSM was warranted.

MiR-30a and miR-205 are downregulated in hypoxia and modulate radiosensitivity of prostate cancer cells by inhibiting autophagy via TP53INP1.

OBJECTIVE: MiR-30a and miR-205 are two miRNAs downregulated in prostate cancer and are involved in autophagy regulation. However, how they are downregulated in prostate cancer is still not clear. In this study, we firstly investigated the association between miR-30a and miR-205 downregulation and hypoxia in prostate cancer. Then, we further investigated the regulative effect of miR-30a on TP53INP1 and autophagy-related radiosensitivity of process cancer cells. MATERIALS AND METHODS: The expression change of miR-30a, miR-205 and Dicer after hypoxic treatment were measured in DU145 and LNCaP cells. The effect of miR-30a and miR-205 on irradiation-induced autophagy and radiosensitivity of the cancer cells were also explored. The regulative effect of miR-30a on TP53INP1 expression and the effect of miR-30a/miR-205/TP53INP1 axis on autophagy and radiosensitivity regulation were further studied. RESULTS: MiR-30a and miR-205 were downregulated under hypoxia as a result of impaired Dicer expression in DU145 and LNCaP cells. Enforced miR-30a and miR-205 expression attenuated irradiation-induced autophagy and also sensitized the cells to irradiation. Dual luciferase assay and following Western blot analysis showed that miR-30a directly targets 3'UTR of TP53INP1 and decreases its expression at protein level. Both miR-30a and miR-205 modulate radiosensitivity of prostate cancer cells at least via TP53INP1. CONCLUSIONS: This study revealed that miR-30a and miR-205 are two hypoxia responsive miRNAs, which simultaneously target TP53INP1 and suppress its expression. The miR-30a/miR-205/TP53INP1 axis is involved in autophagy and radiosensitivity regulation, which represents a potential therapeutic target for the treatment of prostate cancer.

Role of Bcl-2 family members in caspase-3/9-dependent apoptosis during Pseudomonas aeruginosa infection in U937 cells.

Pseudomonas aeruginosa is a gram-negative opportunistic pathogen that is cytotoxic towards a variety of eukaryotic cells. To investigate the effect of this bacterium on monocyte, we infected human U937 cells with the P. aeruginosa strain in vitro. To explore the expression of Bcl-2 and Bax as well as caspase-3/9 activation in the apoptosis of human U937 cells induced by P. aeruginosa, Hoechst 33258 staining and Giemsa staining as well as Flow cytometry analysis were used to determine the rate of apoptosis, and the expressions of Bcl-2 and Bax were assayed by RT-PCR and Western blotting respectively. Bax protein conformation change was assayed by immunoprecipitation. Cytochrome c release was measured by Western blotting. Moreover, exposure of U937 cells to P. aeruginosa measured caspase-3/9 activity. It was found that the apoptosis of human U937 cells could be induced by Pseudomonas aeruginosa in a dose- and time-dependent manner. Also, there were a tendency of alterations with an increased expression level of Bax and a reduced expression level of Bcl-2, increased levels of cytochrome c release, and also with an increased activation of caspase-3/9 and Bax protein conformation change. For the evaluation of the role of caspases, caspase-3/9 inhibitors Z-DEVD-FMK and Z-LEHD-FMK respectively were used. The results were further confirmed by the observation that the caspase inhibitors Z-DEVD-FMK and Z-LEHD-FMK blocked P. aeruginosa-induced U937 apoptosis. It is concluded that P. aeruginosa can induce apoptosis with an up-regulated expression of Bax and a down-regulated expression of Bcl-2, which resulted in increased levels of cytochrome c release and increased caspase-3 and -9 in human U937 cells.

[Analyses of chromosomal karyotypes and cytogenetic variations of animal cell lines].

After the master cell stock(mcs) and working cell bank of more than 30 different strains of 7 animal kidney cell lines (F-81 or CRFK cell line, MDCK cell line, Vero or Vero-2 cell line, MA-104 cell line and BHK-21 cell line) were established in China, the chromosomal number variations and structural aberrations of the above lines, primary feline or canine kidney cell (FKC or CKC) and HeLa cell line were investigated and their karyotypes of routine or Giemsa chromosomal bands were analyzed. The carcinogenesis or tumorigenicity testing of these cells in about 700 nude mice and for colony formation in soft agar (SA) and for agglutination under different concentration of plant lectins was carried out. Both tumorigenicity-negative strains of F-81, CRFK, Vero or Vero-2 lines and very-low-tumorigenicity strains of MDCK line were successfully selected and evaluated for the production of canine or feline combination viral vaccines, which are free of infectious agents, and described with respect to cytogenetic characteristics and tumorigenicity. Rate of modal chromosome number represents the ratio of cell number having modal chromosome number to all the split cell number analyzed at random. Rate of difference represents the ratio of difference of the rate of modal chromosome number between mcs (master cell stock) + n and mcs passages. The chromosomal analysis results showed that the ratio of difference of the rate of modal chromosome number between mcs + n and mcs passages was not more than 5%-15% and the structure aberrations was generally 0%-3%, not more than 5%-10%, thus the hereditary character of cell lines is comparatively stable without significant difference between different passages. The genetic characteristics of chromosomal number of cell lines determines their tumorigenicity, but it is species specific. Experimental models were established for the researches on the prevention and prophylaxis of malignant tumors or cancers and their genetically biological characteristics. Tests showed that there was correlation among cell line chromosome number variations, anchorage independence in soft agar, agglutination under plant lectins and tumor-forming ability in nude mice. Since testing in vitro is more economic, simpler, faster, and is thought to be reliable, we recommend plant lectins followed by SA or analysis of karyotypes as the initial means for monitoring tumorigenicity of animal cell line in nude mice.

PEBA regimen (cisplatin, etoposide, bleomycin, and adriamycin) in the treatment of drug-resistant choriocarcinoma.

Twenty-six drug-resistant choriocarcinoma patients were treated with a PEBA regimen (cisplatin, etoposide, bleomycin, and adriamycin), supplemented by radiotherapy or surgery, from January 1988 to June 1992. A total of 80.8% of the patients had received at least four drugs, and 69.2% had received six or more cycles of combination chemotherapy. All of the patients were primarily treated with PEBA chemotherapy, 5 patients underwent hysterectomy, 9 patients received local lung and/or pelvis cobalt-60 irradiation, and 2 patients with brain metastases received whole brain irradiation. Twenty-five patients achieved a complete remission (CR 96.2%), but 7 patients relapsed. One patient with a relapse reentered sustained CR through surgery and further chemotherapy. Another patient who relapsed lives with tumor after local lung irradiation and chemotherapy. Nineteen patients (73.1%) were in sustained CR lasting at least 1 year. The side effects of the PEBA regimen were moderate and tolerable. We think that PEBA is an optimal regimen for the treatment of drug-resistant choriocarcinoma.