[Emphasizing the standard application of toric intraocular lenses].

In the era of refractive cataract surgery, corneal astigmatism is a crucial factor that affects visual quality after cataract surgery. Toric intraocular lenses (IOLs) have a wide correction range, good surgical predictability, minimal damage to the ocular surface, and stable long-term effects, which can significantly improve postoperative visual quality and patient satisfaction. However, there are still several challenges in the clinical application of toric IOLs, including the awareness of astigmatism correction, the accuracy of preoperative biometry, the widespread adoption of the concept of total corneal astigmatism, the management of surgical planning and details, and the control of postoperative residual astigmatism. This article aims to address these issues to further standardize the clinical application of toric IOLs and help improve the overall level of refractive cataract surgery in China.

[Safety and efficacy of toric intraocular lens implantation for more than 5 years].

Objective: To evaluate the clinical safety and efficacy of toric intraocular lens (IOL) implantation for more than 5 years. Methods: This study was a prospective cohort study in which subjects were continuously observed over a two-year period (May 2014 to May 2016) in nine hospitals. The study randomly assigned subjects to two groups using a central dynamic randomization system: the study group, which received Proming® IQ toric IOL implants, and the control group, which received AcrySof® IQ toric IOL implants. The subjects completed a one-year follow-up, during which various measures were taken and evaluated, including visual acuity, IOL rotation, postoperative complications, intraocular pressure, and subjective evaluation (preoperatively and at 1 day, 6 months, 1 year, and 5 years post-surgery). The main statistical analysis methods include the Mann-Whitney U test, independent sample t-test, Wilcoxon signed rank test, paired sample t-test, chi-square test, and Fisher's exact test. Results: A total of 45 eyes (26 in the study group and 19 in the control group) completed the five-year continuous observation period. The mean age of the subjects was (72.07±10.67) years and the mean interval from surgery to the last visit was (5.39±0.47) years. After five years, there were no significant differences in uncorrected distance visual acuity (0.20±0.26 vs. 0.16±0.13, t=0.17,P=0.752), best corrected distance visual acuity[0.00(0.00, 0.20) vs. 0.05±0.10, U=188.00, P=0.880], uncorrected near visual acuity[0.50 (0.20, 0.60) vs. 0.42±0.20, t=0.35, P=0.857], and best corrected near visual acuity (0.13±0.16 vs. 0.17±0.23, U=161.00, P=0.884) between the two groups. However, all measures improved significantly from baseline levels in both groups (all P<0.05). Five years after surgery, no matter objective refraction [(-0.67±0.85) D vs. (-0.73±1.08)D] or subjective refraction[-0.50 (-1.00, 0.00)D vs. (0.69±0.87)D], the degree of cylindrical degree is significantly lower than preoperative corneal astigmatism [(1.27±0.49) D vs. (1.34±0.82) D, all P<0.001]. In addition, there were no significant differences in intraocular pressure, subjective evaluation of visual adverse symptoms, distance vision spectacle independence, or overall satisfaction evaluation between the two groups (all P>0.05). The IOL rotation was 3.0°(1.0°, 6.0°) in the study group and 4.0°(2.0°, 6.0°)in the control group (U=185.50,P=0.574), indicating no significant difference between the groups in terms of rotational stability. Five years after surgery, there were 7 cases of posterior capsular opacification in the study group and 4 cases in the control group. There were no cases of IOL glistening in the study group, but 5 cases (26.32%) were observed in the control group. Conclusions: The long-term effects of Proming® toric IOL implantation in correcting cataracts with regular corneal astigmatism are clear after five years, with few complications and stable results.

[Comparison study for the proportion of underdiagnosed zonulopathy in angle closure glaucoma].

Objective: To analyze the proportion and clinical characteristics of underdiagnosed zonulopathy in angle closure glaucoma (ACG) patients and to explore the related risk factors. Methods: Case-control study. Continuous cases of ACG patients who underwent phacoemulsification combined with intraocular lens implantation and goniosynechialysis surgery [ACG group, including acute angle closure glaucoma (AACG) and chronic angle closure glaucoma (CACG)] from November 1, 2020 to October 31, 2021 and age-related cataract patients who underwent phacoemulsification combined with intraocular lens implantation surgery in the same period (control group) were included. The diagnosis of zonulopathy was determined according to the intraoperative signs such as wrinkles of the anterior capsule during continuous circular capsulorhexis. The proportion of zonulopathy, preoperative diagnosis rate of zonulopathy, demographic characteristics, anterior chamber depth (ACD), axis length, difference of ACD in both eyes (ACD of the contralateral eye minus ACD of the operated eye) were compared between the two groups. The related risk factors were explored. The paired t-test (comparison between two groups of normally distributed data), non-parametric test (comparison between two groups of non-normally distributed data), Chi-square test (categorical variables), univariate and multivariate logistic regression analysis were used. Results: There were 104 ACG patients (104 eyes), including 63 AACG patients (63 eyes) and 41 CACG patients (41 eyes), and 117 controls (117 eyes). There was no significant difference in age (P=0.29) and gender (P=0.07) between the two groups. The ACG group had shallower anterior chamber (P<0.001), shorter axial length (P<0.001) and more ACD difference in both eyes (P<0.001). In the ACG group, the proportion of zonulopathy was 46.2% (48/104), which was significantly higher than that (6.0%, 7/117) in the control group (P<0.001). In the control group, only zonular laxity was found, while in the ACG group, besides the predominant zonular laxity (68.8%, 33/48), there was zonular dehiscence (31.3%, 15/48). The eyes with AACG (57.1%, 36/63) had a higher proportion of zonulopathy than those with CACG (29.3%, 12/41) (P=0.006). In the ACG group, only 14 cases (29.8%) were diagnosed preoperatively according to slit lamp examination and/or ultrasound biomicroscopy. The proportion of underdiagnosed zonulopathy was 70.8% in the ACG group (34/48). A smaller ACD was found to be related to the zonulopathy in the ACG group. All AACG cases with an ACD ≤2.0 mm and CACG cases with an ACD ≤1.9 mm had zonulopathy. Multivariate logistic regression showed that the ACD difference in both eyes (P=0.025) and the diagnosis of ACG (AACG vs. cataract, P<0.001; CACG vs. cataract, P=0.023) were independent risk factors associated with zonulopathy. Conclusions: The proportion of underdiagnosed zonulopathy among ACG patients is high. Better preoperative diagnostic methods for zonulopathy are needed. Zonulopathy is common in ACG patients, especially in AACG patients, suggesting that zonulopathy may be related to the pathogenesis of ACG. The shallower the ACD, the riskier the zonulopathy. ACD differences between two eyes and ACG types (including AACG and CACG) were related risk factors of zonulopathy.(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 11, 2022).

[Safety and efficacy of A1-UV aspheric intraocular lens implantation over the postoperative 5 years].

Objective: To evaluate the clinical safety and efficacy of A1-UV aspheric intraocular lens (IOL) implantation over the postoperative 5 years. Methods: Prospective cohort study. The subjects came from a finished multicenter, randomized and controlled clinical trial with a follow-up period of 1 year from April to November 2012. The clinical research centers were Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Peking University Third Hospital, Tianjin Medical University Eye Hospital, and Daping Hospital of Army Medical University. Cataract patients in the experimental group were implanted with A1-UV type IOL, while cataract patients in the control group were implanted with SN60WF type IOL, and monocular patients were enrolled. From April to May 2018, patients enrolled in the previous study were recalled for follow-up and continued observation. The visual acuity, spherical equivalent, postoperative complications, non-contact intraocular pressure and subjective evaluation results were statistically analyzed preoperatively, at 1 to 2 days, 1 week, 1 month, 3 months, 6 months, 1 year and 5 years after operation. The main statistical methods included Mann Whitney U test, Wilcoxon signed rank test, independent sample t test, chi square test and Fisher exact test. Results: A total of 42 subjects (22 in the experimental group and 20 in the control group) completed 5-year continuous observation. Among the 42 subjects, 28 were female and 14 were male. The age was (70±9) years, and the time from surgery to recall was (5.77±0.19) years. The age, gender distribution, left/right eye distribution, axial length, IOL power and nucleus hardness classification data of the experimental group and the control group were balanced and comparable (all P>0.05). At different visiting time points, there was no significant difference in the best corrected distance visual acuity (BCDVA), best corrected near visual acuity (BCNVA), uncorrected distance visual acuity (UCDVA) and uncorrected near visual acuity (UCNVA) between the groups (all P>0.05). At 5 years after operation, the UCDVA, BCDVA and BCNVA of the two groups were significantly improved compared with the baseline [all P<0.01; UCDVA was improved from 0.75 (0.30 to 1.30) to 0.10 (-0.10 to 0.70) in the experimental group and from 0.75 (0.30 to 1.60) to 0.20 (-0.10 to 0.80) in the control group; BCDVA was from 0.60 (0.10 to 1.00) to 0.00 (-0.10 to 0.54) in the experimental group and from 0.60 (0.10 to 1.60) to 0.10 (-0.10 to 0.50) in the control group; BCNVA was from 0.55 (0.00 to 1.10) to 0.10 (-0.10 to 0.60) in the experimental group and from 0.55 (0.10 to 1.60) to 0.10 (-0.20 to 0.60) in the control group], but there was no significant change in the UCNVA (both P>0.05). There were no significant differences in the spherical equivalent, intraocular pressure, subjective evaluation of visual adverse symptoms, distance vision spectacle independence and comprehensive evaluation of satisfaction between the groups (all P>0.05). In the experimental group, one eye (4.5%) had an abnormal pupil, one eye (4.5%) had an abnormal IOL with a few particles on the surface of the IOL but no glistening, and 3 eyes (13.6%) had posterior capsular opacification (PCO); in the control group, one eye (5.0%) had an abnormal cornea, five eyes (25.0%) had abnormal IOLs [one eye (5.0%) had IOL calcification, and four eyes (20.0%) had IOL glistening], and one eye (5.0%) had PCO with posterior capsular folds and IOL tilt. There was no significant difference in PCO and IOL abnormality between the two groups (both P>0.05), but there was significant difference in the occurrence of IOL glistening (P=0.04). Conclusion: The long-term effect of A1-UV aspheric IOL on improving the UCDVA is stable and good, with high subjective satisfaction of patients, a low incidence of PCO, no glistening and good biocompatibility, over the postoperative 5 years. (Chin J Ophthalmol, 2021, 57: 41-47).

Exogenous 3-Deoxyglucosone-Induced Carbonyl and Oxidative Stress Causes ß-Cells Dysfunction by Impairing Gut Permeability in Rats.

3-Deoxyglucosone (3DG) is a highly reactive dicarbonyl species, and its accumulation evokes carbonyl and oxidative stress. Our recent data reveal the role of 3DG as an independent factor for the development of prediabetes and suggest that intestine could be its novel target tissue. The present study investigated whether exogenous 3DG increases intestinal permeability by triggering carbonyl and oxidative stress, thus contributing to ß-cell dysfunction. Rats were administered 3DG for two weeks by gastric gavage. Then levels of insulin, ROS, MDA, SOD, NLRP3, TNF-α and IL-1ß in blood plasma as well as the ROS level and content of TNF-α and IL-1ß in pancreas were assessed. Also, the expression of E-cadherin and ZO-1 as well as levels of 3DG, protein carbonylation, ROS, TNF-α and IL-1ß in colon were determined. The 3DG-treated rats showed an elevation in systemic oxidative stress (ROS, MDA and SOD) and in inflammation (TNF-α and IL-1ß), decreased plasma insulin level 15 min after the glucose load, and increased levels of TNF-α, IL-1ß and ROS in pancreatic tissue. In colon tissues of the 3DG-treated rats, decreased E-cadherin expression and increased ROS production as well as an elevation of TNF-α and IL-1ß levels were observed. Interestingly, elevation of colon protein carbonylation was observed in the 3DG-treated rats that displayed 3DG deposition in colon tissues. We revealed for the first time that 3DG deposition in colon triggers carbonyl and oxidative stress and, as a consequence, impairs gut permeability. The enhanced intestinal permeability caused by 3DG deposition in colon results in systemic and pancreatic oxidative stress and inflammatory process, contributing to the development of ß-cell dysfunction.

[To exercise caution in developing intraocular lens exchange].

Nowadays cataract extraction combined intraocular lens (IOL) implantation has become the conventional treatment for cataract. Numbers of IOL exchange after cataract extraction combined IOL implantation have been increasing in recent years. As a non-routine surgery, IOL exchange is normally combined with other surgeries and accompanied by some complications to various extents. Is IOL exchange necessary for all abnomal IOLs? Can IOL exchange be avoided? How to avoid IOL exchange? The purpose of this article is to stress the importance of indication of IOL exchange and how to avoid IOL exchange. (Chin J Ophthalmol, 2018, 54: 324-327).

[A multicenter study of the effectiveness and safety of Toric intraocular lens implantation].

Objective: To evaluate the effectiveness and safety of Proming(®)Toric intraocular lens (IOL) in adults with cataract combined with corneal regular astigmatism. Methods: Multicentre, randomized, open and positive parallel controlled clinical study. A total of 121 patients (121 eyes) who had cataract combined with corneal regular astigmatism and met the inclusion criteria were enrolled in 9 hospitals from May 2014 to May 2016. There were 45 males and 76 females and the median age was 71 (42-88) years old. A total of 121 patients (121 eyes) were randomly assigned to the study group and the control group through the Central Randomization System. Sixty patients (60 eyes) of the study group were implanted with Proming(®)Toric IOL (Model: AT1BH-AT6BH) from Eyebright Medical Technology (Beijing) Co., Ltd., and 61 patients (61 eyes) of the control group were implanted with AcrySof (®)IQ Toric IOL (Model: SN6AT2-SN6AT7) from Alcon Laboratories, Inc. The visual acuity, IOL axial position, slit lamp examination, residual astigmatism and contrast sensitivity were recorded at 1 day, 1 week, 1 month, 3 months, 6 months and 1 year postoperatively. Statistical analysis was performed using χ(2) test, independent sample t test, Mann-Whitney U test, Friedman repeated measured ANOVA on ranks and non-parametric 2-factor variance analysis. Results: A total of 118 patients completed 6 months of follow-up, including 59 from the study group and 59 from the control group. The difference between the two groups in terms of the percentage of best corrected distance visual acuity (BCDVA) reaching 20/40 was 1.69% [100% (59/59) vs. 98.31% (58/59) ], and the lower limit of the 95% CI (-1.60%) was greater than -10.00%. A total of 90 patients were followed up for 1 year, including 43 patients from study group and 47 patients from control group. At 1 year after operation, the percentages of the BCDVA up to 20/40 were 97.67%(42/43) in the study group and 97.87% (46/47) in the control group, and there was no significant difference between the two groups (χ(2)=0.00, P=0.95);the percentages of the uncorrected distance visual acuity (UCDVA) up to 20/40 were 81.40%(35/43) in the study group and 82.98%(39/47) in the control group, and there was no significant difference between the two groups (χ(2)=0.04, P=0.84). At 1 year follow-up, the difference of contrast sensitivity at 18.0 c/d under the bright light, dark light, bright glare and dark glare between the two groups was not statistically significant (U=468.50, P=0.17;U=528.00, P=0.28;U=465.50, P=0.19;U=629.00, P=0.39);the difference of residual astigmatism between the two groups was not statistically significant (U=798.50, P=0.08);the difference of IOL rotation degree between the two groups was not statistically significant (U=869.00, P=0.25). There were no severe inflammatory responses nor other complications associated with IOL in both groups at each follow-up point. Conclusion: The visual quality, astigmatism correction effect, rotation stability and safety of Proming(®)Toric IOL for the treatment of cataract combined with corneal regular astigmatism is equivalent to AcrySof(®) IQ Toric IOL. (Chin J Ophthalmol, 2018, 54: 349-356).

[Evaluation of the right ventricular function in patients with pneumoconiosis by echocardiography].

Objective: To investigate right ventricular function in patients with pneumoconiosis, and to provide a basis for quantitative diagnosis and treatment of pneumoconiosis in clinical practice. Methods: A total of 43 patients with pneumoconiosis who were hospitalized consecutively in Shijiazhuang Prevention and Treatment Center for Occupational Diseases from May 2015 to May 2016 were enrolled, and according to the stage of pneumoconiosis, they were divided into stage I group with 16 patients, stage II group with 14 patients, and stage III group with 13 patients. A total of 16 healthy subjects were enrolled as control group. Echocardiography was performed and the relevant parameters were recorded, i.e., right ventricular transverse diameter (RVTD), tricuspid annular plane systolic excursion (TAPSE), and right ventricular myocardial performance index(Tei index). Results: There were significant differences in Tei index and TAPSE between all groups (P <0.05) except between the stage I group and the control group in terms of Tei index (P>0.05) and between the stage I group and the stage II group in terms of TAPSE (P>0.05). Right ventricular Tei index was negatively correlated with TAPSE (r=-0.547,P<0.05). Conclusion: A combination of right ventricular Tei index and TAPSE can be used for early quantitative evaluation of right ventricular function in patients with pneumoconiosis.

[Evaluation of the safety and visual quality after implantation of the domestic made aspheric intraocular lens].

OBJECTIVE: To evaluate the safety and efficacy of the domestic foldable one-piece aspheric intraocular lens (IOL, Model: A1-UV) for the treatment of cataract. METHODS: A prospective randomized controlled clinical research were conducted. One hundred and nineteen cases (119 eyes) of cataract patients were randomly assigned to the study group (58 cases) and the control group (61 cases). The study group were implanted with the domestic made aspheric intraocular lens (Model: A1-UV) and the control group were implanted with imported aspheric intraocular lens (Model: SN60WF, Alcon Laboratories, Inc.). The visual acuity and the slit lamp examination were evaluated 1-2 day, 1 week, 1 month, 3 months, 6 months and 1 year postoperatively. In addition, the contrast sensitivity tests were carried out 3 months, 6 months and 1 year postoperatively. Data were analyzed by chi-square test and independent t-test. RESULTS: 100 patients had completed 1 year of follow-up, among which 49 cases were from the study group and 51 cases were from the control group. No severe inflammation or complications associated with intraocular lens were noted in either group within 1 year follow-up. The mean BCDVA, BCNVA, UCDVA, UCNVA(Log MAR) of the study group and the control group were 0.04±0.11, 0.11±0.17, 0.13±0.20, 0.35± 0.19 and 0.07±0.15, 0.15±0.20, 0.18±0.23, 0.41±0.21 at 1 year postoperatively. No statistically significant differences were noted between groups in mean BCDVA, BCNVA, UCDVA, UCNVA (t=-1.39, P=0.166; t=- 1.25, P=0.216; t=-1.06, P=0.292; t=-1.59, P=0.116) at 1 year postoperatively. And there was no significant difference in visual acuity between the two groups (P>0.05) 1-2 day, 1 week, 1 month, 3 months and 6 months postoperatively. The difference of the contrast sensitivity between the two groups was not statistically significant (P>0.05), besides the contrast sensitivity of the study group was significantly better than the control group at 12c/d, 18 c/d under bright light(t=2.18, P=0.031; t=2.67, P=0.009) at 3 months postoperatively. And the mean contrast sensitivity of the study group and the control group at 12c/d, 18 c/d under bright light were 1.31 ± 0.36, 0.86 ± 0.41 and 1.15 ± 0.40, 0.65 ± 0.44 at 3 months postoperatively. CONCLUSION: The safety and efficacy of the domestic made foldable one-piece aspheric intraocular lens (Model: A1-UV) for the treatment of cataract is equivalent to the imported aspheric intraocular lens (Model: SN60WF).

[Preliminary exploration of modified side overlap with fundoplication by Yamashita (mSOFY) anastomosis technique in laparoscopic proximal gastrectomy].

Objective: To discuss the feasibility and safety of modified side overlap with fundoplication by Yamashita (mSOFY) in laparoscopic proximal gastrectomy. Methods: Using the method of descriptive case series study, the clinical data of 9 patients with upper gastric cancer who successfully performed mSOFY anastomosis from March 2022 to October 2022 in the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University were retrospectively analyzed.The reconstruction steps of mSOFY anastomosis are as follows: (1) Make a small incision on the right side of the esophageal stump and in front of the anterior wall of the gastric stump; (2) The 45mm linear cutting stapler is placed into the preset anastomosis of the esophagus and the remnant stomach, and the esophagus is rotated 90° counterclockwise along the axis, so that the right wall of the esophagus is anastomosed with the remnant stomach, and the stomach wall is sutured to the left side of the esophagus; (3) The common opening of esophagus and remnant stomach was sutured with inverted suture; (4)Suture the left and lower sides of the esophagus with the remnant stomach to make the esophagus flat against the stomach wall; (5) Open the sutured common opening: due to the pressure of the false dome, the posterior wall of the lower esophageal segment was compressed into a valve-like structure. We mainly observing the postoperative reflux and nutritional improvement of the patients, and recording the intraoperative situation and postoperative complications. Results: Nine patients with upper gastric cancer who completed laparoscopic proximal gastrectomy (mSOFY anastomosis) did not have conversion to laparotomy or intraoperative / postoperative complications. The operation time was (169.4±10.4) minutes, the anastomotic reconstruction time was (51.7±7.1) minutes, the intraoperative bleeding volume was (98.9±43.4) ml, and the number of lymph nodes dissected was (27.2±6.7). The patient recovered well after operation, without any complaints related to reflux esophagitis. Postoperative gastrointestinal radiography showed that the anastomosis was smooth, without stenosis and leakage. The serum albumin [(41.6±3.4) L vs. (39.9±2.6) L], prealbumin [(211.3±38.6) mg/L vs. (205.3±36.0) mg/L], and hemoglobin levels [(126.7±13.2) g/L vs. (121.0±9.7) g/L] of patients before and one month after surgery have no statistically significant differences (all P>0.05). Conclusion: mSOFY anastomosis can be used as one of the safe and feasible reconstruction methods in laparoscopic proximal gastrectomy.

Alamandine protects rat from myocardial ischemia-reperfusion injury by activating JNK and inhibiting NF-κB.

OBJECTIVE: The aim of this study was to investigate whether alamandine plays a protective role in myocardial ischemia-reperfusion injury (IRI) by activating C-Jun N-terminal kinase (JNK) and inhibiting the expression of key proteins in nuclear factor-kappa B (NF-κB) pathway. MATERIALS AND METHODS: Twenty-four Sprague Dawley (SD) rats were numbered and divided into three groups using a random number table, including sham operation group (Sham group), myocardial ischemia-reperfusion injury model group (IRI group), and alamandine pretreatment and myocardial IRI treatment (alamandine group), with 8 SD rats per group. Myocardial tissues were collected from each group. The damage of myocardial tissue was detected using hematoxylin-eosin (H&E) and Masson staining. Finally, the expression levels of JNK and NF-κB pathway-related proteins in myocardial tissue of each group were detected by Western blot. RESULTS: Compared with the IRI group, the alamandine treatment significantly improved cardiac function indicators induced by myocardial IRI in rats, including HR, MAP, LVESP, LVEDP, LVdp/dtmax, and -LVdp/dtmax. In addition, the pathological changes and cell damage of myocardium after alamandine pretreatment were significantly alleviated. At the same time, alamandine can significantly reduce the levels of TNF-α, IL-1ß, IL-6, and NO. Finally, Western blot analysis showed that alamandine pre-treatment can protect cardiomyocytes from myocardial IRI by activating JNK phosphorylation and inhibiting the expression of related proteins in the NF-κB signaling pathway. CONCLUSIONS: Alamandine can protect rat from myocardial IRI via activating JNK phosphorylation and inhibiting NF-κB signaling pathway to reduce the inflammatory response.

[Effects of metformin on papillary thyroid carcinoma in nude rats model].

Objective:To establish an subcutaneous xenotransplanted tumor model of papillary thyroid carcinoma (PTC) and investigate the role of metformin in apoptosis of PTC.Method:Model rats were randomly divided into four groups: control group, Met group and Met+DM group. The tumor volumes were recorded each week. Flow cytometry was used to detect the apoptosis rate of tumor. Immunohistochemistry was used to detect CyclinD1 and the cellular proliferative activity index PCNA and Ki-67.Result:Compared to the control group,there were a significant decrease in tumor volume and antitumor effect in Met and Met+DM groups. The apoptosis rate increased in Met and Met+DM groups. While compared with the control group, the expressions of PCNA,CyclinD1 and Ki-67 significantly decreased in Met and Met+DM groups. There was no difference between Met and Met+DM group.Conclusion:The effect of Metformin on inhibiting tumor growth were related with the imbalance of cell proliferation and apoptosis.

[Metformin induced apoptosis of papillary thyroid carcinoma BCPAP cells].

Objective:To investigate the role of metformin in inducing apoptosis of papillary thyroid carcinoma BCPAP cells. Method:Using MTT methods to detect effects of metformin on cell proliferation of BCPAP in different concentrations (0 mmol/L, 1 mmol/L, 5 mmol/L, 10 mmol/L, 20 mmol/L) and time course (0 h, 4 h, 8 h, 16 h, 24 h, 48 h). The experiment was divided into four groups: Con, Met, Met+Sal and Met+DM, flow cytometry to detect the rate of apoptosis of BCPAP. Then detect the protein expressions of CHOP, GRP78 and Caspase-12 of 4 groups by Western blot. Result:Compared with the experimental control group, the percentage of cell proliferation index significantly decreased in metformin (0-20 mmol/L and 0-48 h) treatment group. Compared with the experimental control group, the percentage of apoptosis cells significantly increased in metformin treatment group. Compared with the control group, the protein expressions of GRP78, CHOP and Caspase-12 were significantly increased in Met group; While compared with the Met group, the protein expressions of GRP78, CHOP and Caspase-12 were significantly inhibited in the Met+Sal group. Conclusion:Metformin can induced availably BCPAP cell apoptosis by activating endoplasmic reticulum stress mechanism.

[One case report: Kimura's disease].

A 28 years old man complained with swellen glymph nodes and mass in neck for 1 year.Physical examination shows painless subcutaneous swollen mass in neck.The level of eosinophil granulocyte count was higher than normal in the peripheral blood.The result of B mode ultrasonography shows left submandibular salivary gland were widely swollen and several swollen lymphnodes in neck.Pathological examination displays features of a large number of Lymphoid follicular hyperplasia,eosinophil granulocyte in filtration.Kimura's disease is a benign,rare,chronic inflammatory disorder of unknown etiology,which affects subcutaneous tissues, lymph nodes and salivary glands.It is characterized by a triad of painless subcutaneous mass,increased eosinophilia in the peripheral blood and in tissues with marked increase in serum IgE.Treatments of Kimura's disease include glucocortieoid drug therapy,surgical resection and local radiotherapy.

Bryostatin-1 and 1alpha,25-dihydroxyvitamin D3 synergistically stimulate the differentiation of NB4 acute promyelocytic leukemia cells.

One of the objectives of treatment for patients with acute promyelocytic leukemia (APL) is to induce tumor cell differentiation and block cell proliferation. Acute promyelocytic leukemia cells (NB4) responded to the combination treatment of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] plus phorbol 12-myristate 13-acetate (PMA) and differentiated into monocyte/macrophage-like cells, as well as expressed strong alkaline phosphatase (ALP) activities. Since PMA has limited clinical application due to its tumor-promoting effect, another protein kinase C activator, bryostatin-1, was currently tested for its interaction with 1alpha,25(OH)2D3 to induce NB4 cell differentiation and block cell proliferation. Bryostatin-1 alone, but not 1alpha,25(OH)2D3 alone, significantly inhibited cell proliferation and induced NB4 cell differentiation into monocyte/macrophages; however neither bryostatin-1 nor 1alpha,25(OH)2D3 alone induced ALP expression. Like PMA, bryostatin-1 synergistically interacted with 1alpha,25(OH)2D3 to stimulate ALP expression 30-fold over the control (P < 0.001) and further promote appearance of monocyte/macrophage-like cells. The ALP stimulation was both time- and dose-dependent. Thus, we demonstrate for the first time that the combination of bryostatin-1 and 1alpha,25(OH)2D3 strongly affect NB4 cell differentiation and proliferation. Therefore, this proposed combination treatment may be an alternatively potential therapeutic regimen for APL patients and assay of ALP may be a more sensitive and facile way to monitor the possible remission of APL patients.

Different shapes of the steroid hormone 1alpha,25(OH)(2)-vitamin D(3) act as agonists for two different receptors in the vitamin D endocrine system to mediate genomic and rapid responses.

Vitamin D(3) produces biologic responses as a consequence of its metabolism into 1alpha,25(OH)(2)-vitamin D(3) [1alpha,25(OH)(2)D(3)] and 24R,25(OH)(2)-vitamin D(3). The metabolic production of these two seco steroids and their generation of the plethora of biologic actions that are attributable to the parent vitamin D(3) are orchestrated via the integrated operation of the vitamin D endocrine system. This system is very similar in its organization to that of classic endocrine systems and is characterized by an endocrine gland (the kidney, the source of the two steroid hormones), target cells which possess receptors for the steroid hormones, and a feed-back loop involving changes in serum Ca(2+) that alter the secretion of parathyroid hormone (a stimulator of the renal 1-hydroxylase) which modulates the output by the kidney of the steroid hormones. There are, however, at least two unique aspects to the vitamin D endocrine system. (a) The chemical structures of vitamin D and its steroid hormones dictate that these be highly conformationally flexible molecules present a wide variety of shapes to their biologic environments. (b) It is now believed that 1alpha,25(OH)(2)D(3) produces biologic responses through two distinct receptors which recognize totally different shapes of the conformationally flexible 1alpha,25(OH)(2)D(3). Thus, the classic actions of 1alpha,25(OH)(2)D(3) to regulate gene transcription occur as a consequence of the stereospecific interaction of a modified 6-s-trans bowl-shape of 1alpha,25(OH)(2)D(3) with its nuclear receptor (VDR(nuc)). The ability of 1alpha,25(OH)(2)D(3) to generate a variety of rapid (seconds to minutes) biologic responses (opening of chloride channels, activation of PKC and MAP kinases) requires a planar 6-s-cis ligand shape which is recognized by a putative plasma membrane receptor (VDR(mem)) to initiate appropriate signal transduction pathways. This report summarizes the evidence for the specificity of different ligand shapes and the operation of the two receptor families for 1alpha,25(OH)(2)D(3).

Studies on the mutagenicity of hair dyes made in China.

A total of 13 commercial hair dye products made in China were tested for mutagenicity in 2 short-term bioassays, the histidine-requiring mutants of Salmonella typhimurium (strains TA98 and TA100) and the micronucleus test with mouse bone-marrow polychromatic erythrocyte cells in vivo. The results showed that the 13 hair dyes were not mutagenic in strains TA98 and TA100 with and without S-9. In the micronucleus test, no mutagenic effect was observed.

Application of biochar from sewage sludge to plant cultivation: Influence of pyrolysis temperature and biochar-to-soil ratio on yield and heavy metal accumulation.

Applying biochar products from sewage sludge (SS) pyrolysis as soil amendment for plant cultivation was investigated in this study with special attention paid to heavy metal accumulation in the plants when pyrolysis temperature and biochar-to-soil mass ratio (C:S) were changed. Biochar obtained at four different temperatures were adopted as soil amendment for Allium sativum L. garlic plant cultivation. Experimental results revealed that biochars were rich in nutrient contents and they improved garlic yields. Although contents of heavy metals including As, Zn, Pb, Ni, Cd, Cr and Cu, etc. were elevated in the biochars compared to local soil, they fell within the acceptable limits for land application and SS is a suitable biochar resource, especially biochar produced at 450°C had rich micropores, relatively stable functional groups in structure and rugged surface to contact well with soil, conducive to its usage as a biochar. The garlic grew faster when planted in the biochar-amended soil and had higher final dry matter yields than those planted in the reference soil, especially biochar produced at 450°C corresponding to the highest final yields. The C:S ratio related to the highest garlic yields changed when the pyrolysis temperature was changed and this ratio was 1:4 for the biochar produced at 450°C. General heavy metal accumulation in the garlic occurred only for the most enriched Zn and Cu, and mainly in the roots & bulbs; in addition this bioaccumulation was increasing as leaching from biochar increased but not increasing with C:S ratio. The garlic planted in soil amended with biochar of 450°C contained the lowest level of heavy metals compared to other biochars. Those results indicated that heavy metal accumulation in plants can be inhibited through proper pyrolysis temperature choice and prevention of heavy metal leaching from the SS biochar.

Mitogenic action of hydrochlorothiazide on human osteoblasts in vitro: requirement for platelet-derived growth factor.

Long-term use of hydrochlorothiazide (HCTZ), a common diuretic agent for hypertension, has been associated with increased bone density and reduced hip fracture rates in patients. In this study, we sought to examine whether HCTZ has an anabolic effect on the proliferation of human osteoblasts (derived from either vertebrate or rib bone samples) in vitro. Cell proliferation was determined by [3H]thymidine incorporation and cell number counting. In medium supplemented with 1% bovine calf serum, HCTZ significantly and reproducibly increased [3H]thymidine incorporation and cell number. The stimulatory effect was dose dependent in a biphasic manner, with the maximal stimulation (approximately 60% above control, P < 0.001) seen at 1 microM HCTZ. In fresh serum-free medium, HCTZ was ineffective as a bone cell mitogen, indicating that the bone cell mitogenic activity of HCTZ required a serum growth factor (GF). HCTZ at doses greater than 10 microM was inhibitory in the presence or the absence of serum, presumably because of the cytotoxic effects. The serum requirement for the bone cell mitogenic activity of HCTZ could be replaced with a conditioned medium (conditioned with normal human osteoblasts for 24 hours), or with a mitogenic dose (1 ng/ml) of PDGF. The GF requirement was specific for PDGF, because other bone cell-derived growth factors (i.e., TGFbeta, IGF-I, IGF-II, and bFGF) were unable to replace serum for the bone cell mitogenic activity of HCTZ. In summary, this study shows that (1) HCTZ stimulated the proliferation of normal, untransformed, human osteoblasts in vitro; (2) the bone cell mitogenic effect of HCTZ required the presence of a serum GF; (3) the serum requirement could be replaced with a bone cell GF in conditioned medium; (4) the GF requirement was specific for PDGF. In conclusion, we have demonstrated for the first time that HCTZ has a direct anabolic effect on human osteoblasts in vitro, and that the mitogenic activity is dependent on the presence of PDGF. Because increased bone cell proliferation is a key determinant of bone formation, these observations raise the interesting possibility that HCTZ could act directly on bone cells to stimulate bone formation in patients.