[Effect of corneal e-value on myopia control in children and adolescents with orthokeratology].

Objective: To investigate the influence of corneal e-value on the effectiveness of orthokeratology in controlling myopia in children and adolescents. Methods: A retrospective cohort study was conducted, involving the data from 1 563 myopic patients (1 563 eyes) who underwent orthokeratology at the Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine from June 2015 to August 2021 and adhered to lens wear for at least 2 years. The cohort consisted of 737 males and 826 females with an average age of (10.84±2.13) years. Based on corneal e-value parameters obtained from corneal topography, patients were categorized into a low e-value group (n=425) and a high e-value group (n=1 138). Data on gender, age, parental myopia history, and baseline measures such as spherical equivalent (SE), axial length, and corneal e-value were collected. Differences in axial length change and corneal fluorescein staining rates were compared between the two groups at 1 and 2 years after the start of lens wear. A generalized linear mixed model was established with axial length change as the dependent variable to analyze the correlation between axial length change and baseline corneal e-value. Results: The initial age of the 1 563 myopic patients was (10.84±2.13) years, with a baseline SE of (-3.05±1.30) D. After 1 year of lens wear, the axial length change was (0.20±0.19) mm in the low e-value group and (0.24±0.20) mm in the high e-value group. After 2 years, the changes were (0.38±0.25) mm and (0.43±0.27) mm, respectively, with statistically significant differences (all P<0.05). The incidence of corneal staining after 1 year of lens wear was 9.2% (39/425) in the low e-value group and 14.1% (160/1 138) in the high e-value group. After 2 years, the rates were 15.8% (67/425) and 21.8% (248/1 138), respectively, with statistically significant differences (all P<0.05). After adjusting for parental myopia history, age, SE, and baseline axial length, the baseline corneal e-value was positively correlated with axial length change at 1 and 2 years after lens wear (all P<0.05). Conclusions: Corneal e-value is an independent factor influencing the effectiveness of orthokeratology in controlling myopia. A smaller corneal e-value is associated with slower axial length growth after orthokeratology, indicating better control of myopia in treated eyes.

[Construction of a risk prediction model for diabetes after kidney transplantation based on genome-wide association study].

Objective: To explore the clinical risk factors and susceptibility genes of diabetes after kidney transplantation (PTDM) and construct a risk prediction model for PTDM. Methods: The data of kidney transplant recipients who underwent follow-up in the Affiliated Lihuili Hospital, Ningbo University and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from January 2001 to December 2022 were retrospectively analyzed. The recipients were divided into PTDM group and Non-PTDM group according to whether they were complicated with PTDM. The differences in clinical indicators between the two groups were compared, the risk factors affecting the incidence of PTDM were determined, and susceptibility genes of PTDM were screened by genome-wide association study (GWAS). PTDM risk prediction models based only on clinical indicators (Model 1) and clinical indicators combined with susceptibility genes (Model 2) were established respectively, and the predictive performance of the two prediction models was compared. Finally, the Nomogram of the optimal model was drawn, and the discrimination, calibration and clinical applicability of the model were evaluated. Results: A total of 113 kidney transplant recipients (70 males and 43 females) were included, with an average age of (46.2±10.8) years. There were 51 cases in PTDM group and 62 cases in Non-PTDM group. The related factors screened by GWAS and logistic regression analysis included family history of diabetes (OR=88.912, 95%CI: 5.827-1 356.601, P=0.001), preoperative triglyceride (TG) (OR=1.888, 95 %CI: 1.150-3.098, P=0.012), uric acid (UA) (OR=1.011, 95%CI: 1.000-1.022, P=0.045) and rs802707 (OR=10.046, 95%CI: 1.462-69.042, P=0.019). The area under the curve (AUC) of the receiver operating characteristics analysis (ROC) predicted by Model 1 for PTDM was 0.891 (95%CI: 0.811-0.972), with the sensitivity of 0.889 and the specificity of 0.742. The AUC of ROC curve predicted by Model 2 for PTDM was 0.930 (95%CI: 0.864-0.995), with the sensitivity of 0.885 and the specificity of 0.900. Conclusions: Family history of diabetes, preoperative TG and UA, and rs802707 are significantly associated with the occurrence of PTDM. In addition, the combination of susceptibility genes could improve the predictive ability of clinical indicators for the risk of PTDM.

[Comparison of the effects and safety of dydrogesterone and medroxyprogesterone acetate on endometrial hyperplasia without atypia: a randomized controlled non-inferior phase â ¢ clinical study].

Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ2=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.

MiRNA-616 aggravates the progression of bladder cancer by regulating cell proliferation, migration and apoptosis through downregulating SOX7.

The article "MiRNA-616 aggravates the progression of bladder cancer by regulating cell proliferation, migration and apoptosis through downregulating SOX7, by X. Zhao, D. Li, S.-T. Zhao, Y. Zhang, A. Xu, Y.-Y. Hu, Z. Fang, published in Eur Rev Med Pharmacol Sci 2019; 23 (21): 9304-9312-DOI: 10.26355/eurrev_201911_19423-PMID: 31773697" has been retracted by the authors due to controversial issues in some inconsistencies in the data provided. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19423.

[Research Progress on the Role of Mitochondrial DNA in the Pathogenesis of Chronic Liver Disease].

Mitochondrial DNA is the mitochondria's own genetic material located within the mitochondrial matrix and is involved in cellular metabolism and energy supply. Mitochondrial DNA damage exacerbates oxidative stress by increasing the release of reactive oxygen species, while mitochondrial DNA release also triggers apoptosis and activates immune inflammatory responses through damage-related molecular patterns. Mitochondrial autophagy regulates mitochondrial DNA damage and release through a negative feedback mechanism to maintain intracellular homeostasis. Recent studies have shown that the occurrence and development of chronic liver disease are closely related to mitochondrial DNA-mediated immune inflammatory responses and oxidative stress.

[New development for targeted therapy of non-alcoholic fatty liver disease with thyroid hormone receptor beta].

Non-alcoholic fatty liver disease has now become a common hepatic metabolic disease, but there is no universally approved therapeutic drug on the market, so there is an urgent need to explore relevant therapeutic drugs. Several studies have shown that the thyroid hormone receptor ß, which is specifically expressed in the liver, plays an important role in lipid metabolism. T3 analogs and thyroid hormone receptor ß-specific agonists have been developed for thyroid hormone receptor ß. Many studies have shown that it can inhibit hepatic triglyceride synthesis, increase hepatic cholesterol clearance, reduce lipid deposition, and at the same time partly increase insulin sensitivity, promote glucose metabolism, and improve inflammation. Therefore, it has become a therapeutic drug with great potential for the treatment of non-alcoholic fatty liver disease. Herein, the mechanism, clinical research and drug development status are reviewed in order to provide new ideas for targeted therapy of non-alcoholic fatty liver disease with thyroid hormone receptor ß.

[A survey on sexual needs and factors of HIV risky sexual behaviors among elderly men at different ages in two communities of Qiandongnan Miao and Dong autonomous prefecture].

Objective: To understand sexual needs and factors of risky sexual behaviors among elderly men at different ages in two communities of Qiandongnan Miao and Dong autonomous prefecture and provide basis for targeted HIV prevention and intervention. Methods: Two communities in the prefecture were selected as study sites. Questionnaire surveys were carried out among elderly men aged 50 and over who visited or consulted in the communities from June to December 2018, and they were tested for HIV and syphilis antibodies. Results: Among 400 elderly men, 209 (52.2%) were 50-64 years old, and 191(47.8%) were above 65 years old. They were mainly Miao people, accounting for 66.3% (265/400), and 235 (58.8%) had an education no more than 6 years. HIV awareness of the two age groups were only 25.8% (54/199) and 26.2% (50/191), respectively. Among those aged 50-64, 142 (68.0%) felt normal sexual desire, and 153 (73.6%) reported penile erections or erections in most cases whenever sex, and 52.9% (110) ejaculated most of the time. HIV prevalence was 1.0% (4/400). Compared with the over 65-year-old group, the proportion of having sex with spouse/stable partners (89.5%, 179/200), proportion of no condom use with their spouse/stable sexual partners during the most recent sex (93.8%, 168/179), proportion of having casual sex (11.0%, 23/209) and commercial sex (3.8%, 8/209) were all higher among 50-64 age group. In comparison to those aged over 65 years old, average monthly income>3 000, and use of sex helper, aged 50-64 (OR=2.70, 95%CI: 1.22-5.95), average monthly income ≤1 000 yuan (OR=2.79, 95%CI: 1.25-6.21), and no use of sex helper (OR=3.78) (95%CI: 1.65-8.67) were related factors of HIV risky sexual behavior last time. Conclusion: Elderly men in the minority prefecture had low HIV awareness. Compared with those≥65 years old, the 50-64 age group had more active sexual behaviors and higher sexual needs. Those from 50-64 age group, with lower economic level and good sexual ability were more likely to have HIV risky sexual behaviors.

[Brief discussion on the taboo and application of stem cell transplantation in the treatment of liver cancer].

Liver cancer is the second-highest mortality cancer in China. It is highly occult, and there is no effective treatment so far. In recent years, stem cell transplantation, especially mesenchymal stem cell (MSCs) transplantation, has been widely used in the treatment of various diseases. Nevertheless, the industry has reached a consensus that malignant tumors are the forbidden area of this transplantation therapy. This is closely related to the two main characteristics of stem cells themselves, namely "self-renewal" and "pluripotency". The following is an overview of the reasons why stem cells, especially MSCs, have become taboo in tumor treatment and their potential application methods, so as to provide some references for further research on this therapy.

PAX3 silencing suppresses gastric cancer proliferation and angiogenesis via MET/PI3K signaling.

PAX3 is the key factor in cell signal transduction pathway and may be involved in the regulation of cancer cell proliferation, differentiation and migration. The aim of the study was to investigate the effects and mechanism of PAX3 silencing on the gastric cancer. Specific PAX3 silencing was performed both in vitro and in vivo using small-interfering RNAs (siRNAs). The proliferation, apoptosis and angiogenesis of gastric cancer cells were assessed using MTT assay, flow cytometry and in vitro tube formation assay. Mice with gastric xenografts, which expressed either si-PAX3 or non-coding siRNA (si-NC), were developed and the effects of PAX3 silencing on tumor progression were evaluated. PCNA is a proliferating cell nuclear antigen and can be used as an index for evaluating cell proliferation status. Immunocytochemistry assay was used to quantify PAX3 and PCNA expression. After 4 weeks of tumor inoculation, tumor tissues were weighed. Tumor tissue morphology and apoptosis were evaluated using HE staining and TUNEL assay. In order to investigate the effect of silencing PAX3 on cell apoptosis, angiogenesis and MET/PI3K pathway, quantitative real-time PCR (qRT-PCR) or western blot were used to detect the expression levels of caspase-3, VEGF, MET, p-MET, PI3K and p-PI3K. After PAX3 silencing, PAX3 expression was significantly decreased in two gastric cancer cell lines, MKN-28 and SGC-7901 (p<0.05 vs Control). PAX3 silencing reduced cell proliferation, induced cell apoptosis and inhibited tube formation. PAX3 and PCNA expression were also significantly decreased. In mice, silencing PAX3 significantly inhibited tumor growth and decreased microvessel density in tumor. PAX3 silencing also decreased cell density in tumors, which concurred with increased apoptosis and PAX3 expression. PAX3 silencing upregulated the expression of caspase-3, downregulated the expression of VEGF, phosphorylation of PI3K and MET. Our data showed that these anti-tumor effects of PAX3 silencing might be attributed to its role in inducing cell apoptosis and inhibiting angiogenesis.

MiRNA-616 aggravates the progression of bladder cancer by regulating cell proliferation, migration and apoptosis through downregulating SOX7.

OBJECTIVE: To investigate the regulatory effect of microRNA-616 (miRNA-616) on cellular behaviors of bladder cancer and the potential mechanism. PATIENTS AND METHODS: The expressions of miRNA-616 and SOX7 in bladder cancer tissues and cell lines were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between miRNA-616 and SOX7 was assessed through Dual-Luciferase Reporter Gene Assay. The regulatory effects of miRNA-616 and SOX7 on cellular behaviors of bladder cancer were evaluated through cell counting kit-8 (CCK-8), colony formation, transwell migration assay, and flow cytometry. RESULTS: MiRNA-616 was upregulated, whereas SOX7 was downregulated in bladder cancer tissues and cell lines. The silence of miRNA-616 attenuated the proliferative and migratory abilities, arrested cell cycle progression in the G2 phase, and stimulated apoptosis in UMUC3 and T24 cells. SOX7 was the target gene of miRNA-616, and its level was negatively regulated by miRNA-616. The knockdown of SOX7 enhanced the proliferative and migratory abilities, and attenuated apoptosis of bladder cancer cells. CONCLUSIONS: MiRNA-616 accelerates bladder cancer cells to proliferate and migrate and inhibits apoptosis by downregulating SOX7. MiRNA-616/SOX7 may be potential therapeutic targets for bladder cancer.

[Prognostic factors of multi-drug resistant organism infection in infected pancreatic necrosis patients].

Objective: To investigate the prognostic factors of multi-drug resistant organism (MDRO) infection in patients with infected pancreatic necrosis(IPN). Methods: A retrospective study was performed to assess the MDRO in IPN patients. The clinical data of 104 IPN patients admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from June 2013 to January 2019 were analyzed. Fifty-six patients were allocated in the MDRO group and 48 patients in the non-MDRO group depended on drug sensitivity test. There were 37 males and 19 females in the MDRO group with age of 40 (23) years. The duration time was 3(5) days between onset and admission. In the non-MDRO group,34 males and 14 females were included with age of (42±14)years. The duration time was 3(4) days between onset and admission. Normally distributed quantitative variables was represented by x±s, non-normally distributed quantitative variables was represented by M(Q(R)). Wilcoxon rank-sum test and χ(2) test were used to analyze the data. Univariate and multivariable Logistic regression analytic model were used to figure out the risk factors associated with MDRO infection. Results: The mean duration of hospital stay was 29.5(31.8) days and hospitalization expenses were CNY 166 991(270 692), which were much higher than those in non-MDRO group (16.5(15.7) days, 56 789(62 354) yuan) (W=1 889, 2 019, both P<0.01). Gram-negative isolates(67.2%, 80 /119) were commonly detected in IPN patients. Acinetobacter baumannii was the most common MDRO(27.0%,20/74). Initial use of carbapenem(OR=2.22, 95%CI: 1.02-4.96, P=0.047) and open necrosectomy(OR=10.00, 95%CI: 3.14-44.77, P<0.01) were the potential risk factors for MDRO-induced infections in IPN. Furthermore, the Logistic regression analysis revealed that open necrosectomy is the independent variable for MDRO infections (OR=9.42, 95%CI: 2.92-42.42, P<0.01). Conclusion: Open necrosectomy was the independent risk factor for the infection of MDRO.

[Research progress of stearoyl-CoA desaturase-1 on obesity and non-alcoholic fatty liver disease Abstract].

Stearoyl-CoA desaturase-1 (SCD-1) is the key rate-limiting enzyme to catalyze the conversion of saturated fatty acids to monounsaturated fatty acids. The monounsaturated fatty acids in the catalytic products are important substrates for the formation of triglycerides, cholesteryl esters and phospholipids. Therefore, SCD-1 plays an important regulatory role in the metabolic process of fat. Currently, obesity and non-alcoholic fatty liver disease are widely prevalent worldwide. SCD-1 has gradually become a potential drug target for the treatment of such diseases due to its important regulatory role in fat metabolism. We summarize the recent research progress of SCD-1 in obesity and non-alcoholic fatty liver disease and the developmental status of SCD-1 inhibitors in order to provide new ideas and references related to disease and target drugs.

[Influence of gender, age and season on thyroid hormone reference interval].

Objective: Using clinical "big data" , to investigate the factors that affect the levels of thyroid hormones, and to explore the partitioning criteria for reference intervals (RI) of these hormones. Methods: An observation study was conducted. Information of 107 107 individuals undergoing routine physical examination in Peking Union Medical College Hospital from September 1(st,) 2013 to August 31(st,) 2016 was collected, thyroid hormone of these subjects were detected. To explore the test results distribution and differences of TSH, FT4 and FT3 by gender and age; according to the seasonal division standard of China Meteorological Administration, the study period was divided into four seasons, and the seasonal fluctuation on TSH was analyzed.To define the appropriate partition by gender, age and season according to significant difference analysis. Results: In male and female, the distributions of TSH were 1.779(0.578-4.758), 2.023(0.420-5.343)mU/L, respectively, and the level of TSH in female was higher than in male (Z=-37.600, P<0.001). The distributions of FT4 were 0.127(0.098-0.162), 0.117(0.091-0.151) µg/L, the distributions of FT3 were 3.33(2.47-3.74), 3.01(2.35-3.57)ng/L. And the level of FT4, FT3 in female were significantly lower than in male (Z=-94.000, -154.600, all P<0.001). Furthermore, males were divided into two groups by 65 years old and female were divided by 50 years old, respectively, and the distributions of TSH in male and female of older group were 1.818(0.528-5.240), 2.111(0.348-5.735)mU/L, in younger group were 1.778(0.582-4.696), 1.991(0.427-5.316)mU/L. The level of TSH in older group was significantly higher than in younger group (Z=-2.269, -10.400, all P<0.05), and the distribution of TSH in older group was much wider than in younger. The distribution of whole in spring, summer and autumn was 1.869( 0.510-5.042)mU/L, in winter was 1.978(0.527-5.250) mU/L, and the difference between them had statistical significance (Z=-15.000, P<0.001). Conclusions: Gender and age significantly affect the serum levels of TSH, FT4, and FT3, the distribution of TSH in female and elder group are wider than in male, and that of FT4, FT3 are lower.Seasons significantly affect the serum TSH level, the peak value is observed in winter. There are obviously differences between "rough" RIs and manufacture recommended RIs. Each laboratory should establish reference intervals for thyroid hormones on the premise of appropriate grouping.

[Study on the role of NALP3 inflammasome in Porphyromonas gingivalis lipopolysaccharide induced RAW264.7].

Objective: To illuminate the effect of NALP3 inflammasome on regulating the expression of cytokines of macrophages in periodontitis. Methods: RAW264.7 cells were cultured and divided into three groups. The first group stayed normal as control, the second group was stimulated by 1 mg/L Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS), the third group was pretreated with AC-YVAD-CMK (caspase-1 inhibitor) before stimulated with 1 mg/L Pg LPS. RAW264.7 cells pretreated with various concentrations (0, 5, 10, 25, 50, 75, 100, 200 µmol/L) of AC-YVAD-CMK for 2 h, and stimulated by 1 mg/L Pg LPS for 24 h in the third group. After that, cell survival rate were detected by cell counting kit-8. Every group cells gene transcription of NALP3 and interleukin-1ß (IL-1ß) were detected by quantitative real-time PCR (qPCR) after 6 h, protein expression of NALP3 and IL-1ß were separately detected by Western blotting and enzyme linked immunosorbent assay (ELISA) after 24 h, respectively. Results: It is observed that treatment with 5, 10, 25, 50, 75, 100, 200 µmol/L AC-YVAD-CMK did not significantly affect the viability of RAW264.7 cells. qPCR showed that mRNA expression of IL-1ß level (1.03±0.08, 5.48±0.22, 4.31±0.20) and NALP3 level (0.96±0.05, 2.62±0.44, 1.73±0.09). Western blotting showed that protein expression of NALP3 level (1.00±0.10, 2.34±0.04, 1.64±0.04), ELISA showed protein secretion of IL-1ß level ([40.20±0.25], [61.50±1.81], [52.40±1.91] ng/L). After stimulated by Pg LPS, mRNA and protein expression of IL-1ß (P<0.01, P<0.01) and NALP3 (P<0.01, P<0.01) significantly increased; but the expression of IL-1ß (P=0.002, P=0.027) and NALP3 (P<0.01, P<0.01) were decreased when pretreated with AC-YVAD-CMK. Conclusions: NALP3 inflammasome signal pathway can be activated by Pg LPS in RAW264.7. Block of the pathway can inhibit Pg LPS-induced secretion of cytokines.