Antihypertensive medication and dementia risk in patients with hypertension: A nationwide population-based study.

The claim between hypertension and dementia needs more evidence due to limited data. We aim to examine the risk of dementia in patients with hypertension, and determine whether the use of antihypertensive medications (AHMs) could decrease the incidence of dementia diagnosed following the onset of hypertension. We employed the Taiwan National Health Insurance Research Database from 2000 to 2016 and performed a retrospective cohort study. We also carried out a case-control study to see if AHMs could reduce the incidence of newly diagnosed dementia in hypertensive patients. In the retrospective cohort study, we selected 587,762 participants with age and gender matched in experimental and control groups. The hypertension group had significantly higher adjusted hazard ratios (aHRs) of getting newly diagnosed dementia, including all-cause dementia, Alzheimer's disease, and vascular dementia (aHR, 2.86; 95 % confidence interval (CI), 2.74-2.99) than the control group. Three kinds of specific AHMs, namely, angiotensin II receptor blockers (aHR, 0.55; 95 % CI, 0.53-0.57), calcium channel blockers (aHR, 0.76; 95 % CI, 0.73-0.80), and diuretics (aHR,0.93; 95 % CI, 0.89-0.97) could significantly decrease the incidence of getting newly diagnosed dementia. Also, the application of traditional Chinese medicine (TCM) significantly associates with the lower aHRs of newly diagnosed dementia in hypertensive patients compared to patients without TCM (aHR, 0.90; 95 % CI, 0.81-1.00). Hypertension may be a significant risk factor for dementia. Both AHMs and TCM significantly associate with the lower incidence of newly diagnosed dementia in hypertensive patients.

Epstein-Barr Virus Uveitis Confirmed via Aqueous Humor Polymerase Chain Reaction and Metagenomics-A Case Report.

This is a case report of Epstein-Barr virus (EBV) uveitis confirmed via aqueous humor polymerase chain reaction (PCR) and metagenomics. This 72-year-old male with a history of diabetes and herpes zoster complained of redness and blurred vision in his right eye for eight months. Mild conjunctival injection, anterior chamber cells, mutton-fat keratic precipitates, and vitreous haze were noted. Fluorescein angiography revealed dye leakage from retinal vessels without retinal ischemic changes. Only the serum anti-cytomegalovirus (CMV) IgG was positive while the aqueous humor PCR for VZV (Varicella-zoster virus), HSV (Herpes simplex viruses), CMV, and EBV was initially negative. Inflammation recurred and vitreous haze worsened after discontinuing nine-month topical ganciclovir and oral prednisolone. the aqueous humor PCR was repeated due to persistent low-grade inflammation. The EBV PCR turned out to be positive. Shotgun metagenomics revealed 1459 classified sequences (1.62%) and confirmed the EBV infection. Topical ganciclovir and methylprednisolone treatment was resumed. Conjunctival injection improved while pigmented keratic precipitates lessened. Elderly patients with diabetes or under immunosuppression may be susceptible to chronic uveitis associated with subsequent EBV infection. Repeated aqueous humor PCR and shotgun metagenomics are important tools in the diagnosis of this case of chronic indolent panuveitis.

Long-term exposure to air pollution and risk of Sarcopenia in adult residents of Taiwan: a nationwide retrospective cohort study.

BACKGROUND: Sarcopenia is an age-related, multifactorial syndrome. Previous studies have shown that air pollutants are associated with inflammation and oxidative stress. However, the association between long-term exposure to air pollution and sarcopenia is not completely understood. METHODS: The Taiwan National Health Research Database (NHIRD) contains medical records of almost all Taiwanese residents. Daily air pollution data collected by the Taiwan Environmental Protection Agency was used to analyze concentrations of sulfur oxide (SO2), carbon monoxide (CO), nitrogen monoxide (NO), nitrogen dioxide (NO2), and particulate matter (PM2.5, PM10). The databases were merged according to the insurants' living area and the location of the air quality monitoring station. We categorized the pollutants into quartiles (Q1, Q2, Q3, and Q4). RESULTS: Our study population consisted of 286,044 patients, among whom 54.9% were female and 45.1% were male. Compared to Q1 levels of pollutants, Q4 levels of SO2 (adjusted hazard ratio [aHR] = 8.43; 95% confidence interval [CI] = 7.84, 9.07); CO (aHR = 3.03; 95%CI = 2.83, 3.25); NO (aHR = 3.47; 95%CI = 3.23, 3.73); NO2 (aHR = 3.72; 95%CI = 3.48, 3.98); PM2.5 (aHR = 21.9; 95% CI = 19.7, 24.5) and PM10 (aHR = 15.6; 95%CI = 14.1, 17.4) increased risk of sarcopenia. CONCLUSIONS: Our findings indicated a significantly increased risk of sarcopenia in both male and female residents exposed to high levels of air pollutants.

Short-Term Effects of Brolucizumab in the Treatment of Wet Age-Related Macular Degeneration or Polypoidal Choroidopathy Refractory to Previous Anti-Vascular Endothelial Growth Factor Therapy.

Background and objectives: To report the initial response to a single intravitreal brolucizumab (IVI-B) injection in wet age-related macular degeneration (wAMD) or polypoidal choroidopathy (PCV) complicated with either persistent subretinal fluid (SRF) or pigment epithelial detachment refractory to previous anti-vascular endothelial growth factor (anti-VEGF) therapy. Material and methods: In this retrospective study, all eyes received a single IVI-B (6 mg/0.05 mL) for wAMD or PCV with treatment-resistant SRF or PED. Outcome measures included assessment in central retinal thickness (CRT), visual acuity, and evaluation for changes in the SRF or PED on OCT. Follow-up was prior to the first brolucizumab injection, then at 1 week and 5 weeks afterwards. Results: In total, 10 eyes of 10 patients (6 women [60%]) were enrolled. Five patients had wAMD and five patients had PCV. Average age of participants was 67.6 years. All patients received one IVI-B. All patients were not treatment-naïve to anti-VEGF agents. At the first week and fifth week following the first IVI-B, seven out of seven patients (100%) had resolved SRF. However, seven out of nine patients (78%) had no improvement of their PED at 5 weeks follow-up. Mean PED height and width before the first IVI-B was 339.77 µm and 2233.44 µm, respectively. Mean PED height and width at the fifthweek following the first IVI-B was 328.125 µm and 2129.5 µm, respectively. Overall mean visual acuity before the first IVI-B was 0.224; and 5 weeks following the first IVI-B was 0.38. Conclusions: Treatment with brolucizumab resulted in anatomical improvement for all patients with persistent SRF. Limited efficacy was seen for persistent PED. Brolucizumab appears to be a safe and effective option for treatment-resistant SRF. Future multicenter collaborative studies are warranted.

Short-term anatomic response of the choroid to tropicamide in myopic patients.

We aimed to investigate how tropicamide alters subfoveal choroidal thickness (SFChT) and choriocapillaris flow density (CD) and determine the predictive factors of choroid thickness and vascular density in myopic eyes. This retrospective study was conducted from September 2018 to March 2019. SFChT was measured with enhanced depth spectrum-domain optical coherence tomography. The choriocapillaris was imaged using optical coherence tomography angiograms. Ocular parameters were measured thirty minutes before and after 1% tropicamide instillation. Twenty-five eyes of 15 patients (mean age 38.12 ± 6.35 years old and refractive error-8.57 ± 3.37 D) met the study criteria. The baseline linear regression model showed an association of thinner choroid with older age (P = .027) and high myopic patients (P = .001). Tropicamide substantially increased SFChT (P = .001), but had no significant influence on CD (P = .526). Moreover, SFChT variation after tropicamide instillation positively correlated with diopter changes in spherical equivalent (P = .005) and percentage changes in CD (P = .046). In myopic eyes, choroidal layer thickened substantially in response to tropicamide. The increase of SFChT only correlates with variations in spherical equivalent and CD. Short-term tropicamide installation altered both choroid thickness and choroid microvasculature, which implies an interplay among choroidal volume, perfusion, and ciliary muscle tone.

Intraovarian Injection of Recombinant Human Follicle-Stimulating Hormone for Luteal-Phase Ovarian Stimulation during Oocyte Retrieval Is Effective in Women with Impending Ovarian Failure and Diminished Ovarian Reserve.

It is a challenge to obtain sufficient eggs during in vitro fertilization (IVF) in women with impending ovarian failure (IOF)/diminished ovarian reserve (DOR). Although studies have suggested that more than one wave of follicle growth exists, the efficacy of controlled ovulation stimulation (COS) in both follicular and luteal phases of the same ovarian cycle (DuoStim) is not established in women with IOF/DOR. We investigated the efficacy of DuoStim using the intraovarian injection of recombinant human follicle-stimulating hormone (rhFSH) during oocyte retrieval in women with DOR. For luteal-phase stimulation, intraovarian (Group A, N = 28) or superficial subcutaneous (Group B, N = 18) injection of 300 IU rhFSH immediately after oocyte retrieval was administered as the first dose, and intermittent superficial subcutaneous addition of gonadotropins was employed accordingly for further COS in both groups. In Group A, significantly lower Gn doses, a shorter duration of COS, a greater number of antral follicle counts, and an increased number of retrieved mature and total oocytes were noted. Compared with the clinical outcomes of luteal-phase COS, the average daily doses of rhFSH used in Group A were significantly lower. In summary, the novel approach using intraovarian rhFSH injection provides an efficient treatment regimen in women with IOF/DOR.

Ovarian Follicular Growth through Intermittent Vaginal Gonadotropin Administration in Diminished Ovarian Reserve Women.

It is a challenge to obtain enough oocytes during in vitro fertilization (IVF) in women who have a poor ovarian response (POR) in achieving conception. We have adopted the characteristics of the first uterine pass effect, which we pioneered in employing the vaginal administration of gonadotropins in women receiving IVF treatments. In our previous study employing vaginal administration, faster absorption and slower elimination of gonadotropins were demonstrated, and, female subjects presented proper ovarian follicle growth and pregnancy rates. In this study, during 2016-2020, 300 to 675 IU of gonadotropins were administered vaginally every three days in 266 POR women for their controlled ovarian hyperstimulation (COH). The injections were performed with needles angled at 15-30° towards the middle-upper portions of the bilateral vaginal wall, with an injection depth of 1-2 mm. For the COH results, these women, on average, received 3.0 ± 0.9 vaginal injections and a total dose of 1318.4 ± 634.4 IU gonadotropins, resulting in 2.2 ± 1.9 mature oocytes and 1.0 ± 1.2 good embryos. Among these embryos, 0.9 ± 1.0 were transferred to reach a clinical pregnancy rate of 18.1% and a live birth rate of 16.7%. In conclusion, the intermittent vaginal administration of gonadotropins proved to be effective in POR women for their IVF treatments.

Ethnic disparity in metabolic syndrome and related obesity and health behavior: a community study in Taiwan.

BACKGROUND: As studies on ethnic disparities in metabolic syndrome and its risk factors in Taiwan are still rare, the aims of this study were: (1) to detect the differences in the rates of metabolic syndrome, obesity and health behaviors between two ethnic groups (indigenous Tsou and nonindigenous Han) living in the same area and with similar age and sex distributions; (2) to examine whether ethnicity per se plays a significant role in the occurrence of metabolic syndrome, while taking other risk factors including sociodemographic characteristics, obesity and health behaviors into consideration. METHODS: This is a cross-sectional study using data from a community survey conducted in Chiayi County in southwestern Taiwan. A frequency matching strategy by age and sex with a ratio of 1 (Tsou) to 3 (Han) was applied to select a comparable sample between both ethnic groups (667 Tsou and 2001 Han) from among the survey participants. Furthermore, participants with cardiometabolic diseases diagnosed before the surveyed day were excluded to avoid confounding any associated risk factors for developing metabolic syndrome (MS). A final analytic sample of 1482 remained. The used information included sociodemographic characteristics, medical histories, health behaviors, and the concentrations of triglycerides, cholesterol, and glucose. RESULTS: Indigenous Tsou had significantly higher rates of metabolic syndromes, obesity and unhealthy behaviors than their Han counterparts (MS: 54.0% vs. 29.1%, obesity: 54.0% vs. 23.2%, drinking alcohol: 17.5% vs. 13.6%, and higher intake of fried food: 6.4% vs. 4.4%), even though they were similar in age and sex distributions. The significant risk factors for subsequently developing MS included being indigenous Tsou (adjusted POR = 2.62, P < 0.001), older, single, and obese. Stratified analyses on the risk factors for developing MS by health behaviors and by obese problems also indicated increased risks of being indigenous Tsou. CONCLUSIONS: There existed ethnic differences in the rates of metabolic syndrome, obesity, and health behaviors. Ethnicity per se did play a significant role in developing MS; in particular indigenous Tsou people had increased risks, suggesting possible biological reasons rooted in their origins that need further exploration. In addition, unhealthy behaviors may potentially have an indirect effect on developing MS via their effect on obesity.

Ovarian Folliculogenesis and Uterine Endometrial Receptivity after Intermittent Vaginal Injection of Recombinant Human Follicle-Stimulating Hormone in Infertile Women Receiving In Vitro Fertilization and in Immature Female Rats.

The uterine first-pass effect occurs when drugs are delivered vaginally. However, the effect of vaginally administered recombinant human follicle-stimulating hormone (rhFSH) on ovarian folliculogenesis and endometrial receptivity is not well established. We aimed to compare the efficacy of rhFSH administered vaginally and abdominally in clinical in vitro fertilization (IVF) treatment, pharmacokinetic study, and animal study. In IVF treatment, the number of oocytes retrieved, endometrial thickness and uterine artery blood perfusion were not different between women who received the rhFSH either vaginally or abdominally. For serum pharmacokinetic parameters, significantly lower Tmax, clearance, and higher AUC and T1/2_elimination of rhFSH were observed in women who received rhFSH vaginally, but urine parameters were not different. Immature female rats that received daily abdominal or vaginal injections (1 IU twice daily for 4 days) or intermittent vaginal injections (4 IU every other day for two doses) of rhFSH had more total follicles than the control group. In addition, the serum progesterone and progesterone receptors in the local endometrium were significantly higher in the groups treated with intermittent abdominal or vaginal injection of rhFSH, compared with those who recieved daily injection. In summary, vaginal administration of rhFSH may provide an alternative treatment regimen in women receiving IVF.

Effect of ICD-9-CM to ICD-10-CM coding system transition on identification of common conditions: An interrupted time series analysis.

PURPOSE: To evaluate the effect of diagnostic coding system transition on the identification of common conditions recorded in Taiwan's national claims database. METHODS: Using the National Health Insurance Research Database, we estimated the 3-month prevalence of recorded diagnosis of 32 conditions based on the ICD-9-CM codes in 2014-2015 and the ICD-10-CM codes in 2016-2017. Two algorithms were assessed for ICD-10-CM: validated ICD-10 codes in the literature and codes translated from ICD-9-CM using an established mapping algorithm. We used segmented regression analysis on time-series data to examine changes in the 3-month prevalence (both level and trend) before and after the ICD-10-CM implementation. RESULTS: Significant changes in the level were found in 19 and 11 conditions when using the ICD-10 codes from the literature and mapping algorithm, respectively. The conditions with inconsistent levels by both of the algorithms were valvular heart disease, peripheral vascular disease, mild liver disease, moderate to severe liver disease, metastatic cancer, rheumatoid arthritis and collagen vascular diseases, coagulopathy, blood loss anemia, deficiency anemia, alcohol abuse, and psychosis. Nine conditions had significant changes in the trend when using the ICD-10 codes from the literature or mapping algorithm. CONCLUSIONS: Less than half of the 32 conditions studied had a smooth transition between the ICD-9-CM and ICD-10-CM coding systems. Researchers should pay attention to the conditions where the coding definitions result in inconsistent time series estimates.

Age, Initial Central Retinal Thickness, and OCT Biomarkers Have an Influence on the Outcome of Diabetic Macular Edema Treated With Ranibizumab- Tri-center 12-Month Treat-and-Extend Study.

Objective: We report the tri-center 1-year outcomes of a treat-and-extend (T&E) regimen in four-week intervals with ranibizumab for diabetic macular edema (DME). Methods: In this retrospective study, all eyes received 3 monthly loading injections of 0.5 mg ranibizumab, followed by a T&E regimen for DME. Regression models were used to evaluate the associating factors for visual and anatomical outcomes. Results: Ninety one eyes from 64 patients were enrolled. Mean LogMAR best-corrected visual acuity (BCVA) improved from 0.58 at baseline to 0.36 at month 12 and mean central retinal thickness (CRT) decreased from 411 µm at baseline to 290 µm at month 12. Younger age and eyes having thinner baseline CRT, with ellipsoid zone disruption (EZD), and without epiretinal membrane (ERM) were associated with better final CRT. Moreover, eyes with thicker baseline CRT tend to receive more injections. Among the parameters, only having ERM or EZD was associated with significant BCVA recovery. Conclusions: A T&E regimen with ranibizumab by 4-week intervals is effective in improving BCVA and reducing CRT with efficacy notable starting from the third month. Clinical parameters including age, initial CRT, and presence of ERM or EZD significantly influenced therapeutic outcomes. Moreover, the presence of ERM should not preclude DME patients from receiving anti-VEGF therapy. Future studies with larger cohorts are warranted.

Preliminary Evaluation of a Novel Microwave-Assisted Induction Heating (MAIH) System on White Shrimp Cooking.

The microwave-assisted induction heating (MAIH) system provides comprehensive heating by combining microwave heating (with 1300 W of power and 2450 MHz of frequency) in the top part and induction heating (with 1800 W of power) in the bottom part. In this study, fresh white shrimps were placed in a sealed crystallized polyethylene terephthalate (CPET) container and heated in the MAIH system at two temperatures (130 and 90 °C) from 60 to 120 s. Afterwards, the shrimp samples were rapidly cooled, and the changes in the shrimp quality, including the appearance, cook loss, aerobic plate count (APC), color values, and texture, during the heating process were analyzed. The results demonstrate that longer heating times decrease the APC levels, but increase the cook loss, color values (lightness, redness, and whiteness), and texture (hardness, cohesiveness and chewiness) of the white shrimp samples. In particular, the white shrimp is fully cooked and gains a completely red appearance, along with no APC detected after heating in the MAIH system at 130 °C for at least 80 s or at 90 °C for at least 100 s. In summary, to achieve a good appearance, no APC detected, and low cook loss, the following heating conditions are recommended for cooking white shrimp in the MAIH system: heating at 130 °C for 80 s or at 90 °C for 100 s. This novel MAIH technology allows food to be heated and sterilized after being packed, thereby eliminating the post-pollution issue. To the best of the authors' knowledge, this is the first study to evaluate the use of MAIH in the application of food processing.

Changes in striatal dopamine transporters in bipolar disorder and valproate treatment.

BACKGROUND: Previous studies suggested that a disturbance of the dopamine system underlies the pathophysiology of bipolar disorder (BD). In addition, the therapeutic action of medications for treating BD, such as valproate (VPA), might modulate dopamine system activity, but it remains unclear. Here, we aimed to investigate the role of the striatal dopamine transporter (DAT) in BD patients and in social defeat (SD) mice treated with VPA. METHODS: We enrolled community-dwelling controls (N = 18) and BD patients (N = 23) who were treated with VPA in a euthymic stage. The striatal DAT availabilities were approached by TRODAT-1 single photon emission computed tomography. We also established a chronic SD mouse model and treated mice with 350 mg/kg VPA for 3 weeks. Behavioral tests were administered, and striatal DAT expression levels were determined. RESULTS: In humans, the level of striatal DAT availability was significantly higher in euthymic BD patients (1.52 ± 0.17 and 1.37 ± 0.23, p = 0.015). Moreover, the level of striatal DAT availability was also negatively correlated with the VPA concentration in BD patients (r = -0.653, p = 0.003). In SD mice, the expression of striatal DAT significantly increased (p < 0.001), and the SD effect on DAT expression was rescued by VPA treatment. CONCLUSIONS: The striatal DAT might play a role in the pathophysiology of BD and in the therapeutic mechanism of VPA. The homeostasis of DAT might represent a new therapeutic strategy for BD patients.

Accuracy augmentation of body composition measurement by bioelectrical impedance analyzer in elderly population.

Bioelectrical impedance analysis (BIA) is currently the most commonly used method in clinical practice to measure body composition. However, the bioelectrical impedance analyzer is not designed according to different countries, races, and elderly populations. Because different races may have different body compositions, a prediction model for the elderly population in Taiwan should be developed to avoid population bias, thereby improving the accuracy of community evaluation surveys.Dual energy X-ray absorptiometry (DXA) was used as a standard method for comparison, and impedance analysis was used for the development of a highly accurate predictive model that is suitable for assessing the body composition of elderly people.This study employed a cross-sectional design and recruited 438 elderly people who were undergoing health examinations at the health management center in the Tri-Service General Hospital as study subjects. Basic demographic variables and impedance analysis values were used in four predictive models, namely, linear regression, random forest, support vector machine (SVM), and eXtreme Gradient Boosting (XGBoost) models, to predict DXA body composition. The data from 354 study subjects were used to develop the predictive model, while the data from 84 study subjects were used to validate the accuracy of the predictive model.The body composition of elderly people as estimated by InBody 720 was highly correlated with that estimated by DXA. The correlation coefficient between InBody 720 and DXA for muscle mass was 0.969, and that for fat mass was 0.935. Consistency analysis results showed that InBody 720 tends to underestimate muscle mass and fat mass. A comparison of the accuracy of the linear regression, random forest, SVM, and XGBoost models showed that the linear regression has the highest accuracy. The correlation coefficient between the new model and DXA for muscle mass and fat mass were 0.977 and 0.978, respectively.The new predictive model can be used to monitor the nutrition status of elderly people and identify people with sarcopenia in the community.

Somatic pain associated with initiation of interferon-alpha (IFN-α) plus ribavirin (RBV) therapy in chronic HCV patients: A prospective study.

OBJECTIVE: This study is aimed to investigate the association between interferon-alpha (IFN-α) plus ribavirin (RBV) treatment and emergence of somatic pain symptoms in patients with hepatitis C virus (HCV) over a 24-week treatment. METHOD: In this prospective cohort study, 297 patients with HCV were evaluated at baseline and 2nd, 4th, 8th, 12th, 16th, 20th, and 24th week with structured Mini-International Neuropsychiatric Interview for Major Depressive Disorder (MDD) diagnosis and the Neurotoxicity Rating Scale (NRS) for somatic symptoms. RESULTS: Eighty-seven out of the 297 patients (29%) developed IFN-α induced depression and had significantly higher somatic pain symptoms as early as the 2nd week and at all the assessment time points (p â€‹< â€‹.001). Most depressed patients perceived greatest somatic pain at the 8th week of treatment. Moreover, NRS somatic pain scores after initial therapy strongly correlated with NRS somatic pain scores at all other assessment time points (p â€‹< â€‹.001). CONCLUSION: IFN-α therapy induce significant somatic pain as early as the 2nd week of treatment in HCV patients who later developed MDD. Thus, initial NRS somatic pain score after initiation of IFN-α treatment may serve as a reference for the susceptibility of the individual to IFN-α induced depression.

Arsenite-induced apoptosis can be attenuated via depletion of mTOR activity to restore autophagy.

Arsenic and its compounds are toxic environmental pollutants and known carcinogens. We investigated here the mechanism of arsenite-induced damage in renal cells. Treating human embryonic kidney cells (HEK293) with sodium arsenite reduces cell viability in a dose- and time-dependent manner. The decline of cell viability is due to apoptotic death since arsenite treatment reduces Akt activity and the Bcl2 level but increases caspase 3 activity and the cytochrome c level. These effects can be reverted by the addition of an apoptosis inhibitor. PTEN, the upstream negative regulator of Akt activity, was also reduced with arsenite treatment. Noticeably, PTEN markedly increased in the insoluble fraction of the cells, suggesting a cell failure in removing the damaged proteins. Arsenite treatment activates a variety of signaling factors. Among them, ERK and JNK are associated with autophagy via regulating the levels of LC3 and p62. With arsenite administration, the LC3 and p62 levels increased. However, lysosomal activity was decreased and led to the decline of autophagic activity. The addition of rapamycin, the mTOR inhibitor, activated the autophagic pathway that accelerated the removal of damaged proteins. The recovery of autophagy increased the viability of arsenite-treated cells. Similar to rapamycin treatment, the knockdown of mTOR expression also enhanced the viability of arsenite-treated cells. Both rapamycin treatment and mTOR knockdown enhanced ERK activity further, but reduced JNK activity and the p62 level in arsenite-treated cells. Lysosomal activity increased with the depletion of mTOR, indicating an increase of autophagic activity. These results reveal the critical role of mTOR in regulating the cell fate of arsenite-exposed renal cells.

Effects of Chinese herbal medicine therapy on survival and hepatic outcomes in patients with hepatitis C virus infection in Taiwan.

BACKGROUND: Chinese herbal medicine (CHM) is a complementary natural medicine that is used widely for the treatment of hepatic diseases. The aim of this study was to investigate the effects of the long-term use of CHM for the treatment of liver diseases, as prescribed by TCM doctors, on overall mortality and hepatic outcomes in patients with HCV. PATIENTS AND METHODS: We identified 98788 patients with HCV. Of these, 829 and 829 patients who were users and non-users of CHM, respectively, were matched for age, gender, CCI, and comorbidities prior to CHM treatment. The chi-squared test, Cox proportional hazard model, Kaplan--Meier method, and log-rank test were used for comparisons. RESULTS: CHM users had a lower risk of overall mortality than non-users after adjustment for comorbidities by using a multivariate Cox proportional hazard model (p-value < 0.001; HR: 0.12, 95% CI: 0.06-0.26). In addition,the CHM users had a lower risk of liver cirrhosis than non-users after adjustment for comorbidities (p-value = 0.028; HR: 0.29, 95% CI: 0.09-0.88). The 12-year cumulative incidences of overall mortality and liver cirrhosis were lower in the CHM group (p-value < 0.05 for both, log rank test). The CHM co-prescription for Dan-Shen, Bie-Jia, Jia-Wei-Xiao-Yao-San => E-Shu was found to occur most often associated for the specific treatment of HCV infection. CONCLUSION: CHM as adjunctive therapy may reduce the overall mortality and the risk of liver cirrhosis in patients with HCV. The comprehensive list of the herbal medicines that may be used for the treatment of patients with HCV may be useful in future scientific investigations or for future therapeutic interventions to prevent negative hepatic outcomes in patients with HCV.

The conserved basic residues and the charged amino acid residues at the α-helix of the zinc finger motif regulate the nuclear transport activity of triple C2H2 zinc finger proteins.

Zinc finger (ZF) motifs on proteins are frequently recognized as a structure for DNA binding. Accumulated reports indicate that ZF motifs contain nuclear localization signal (NLS) to facilitate the transport of ZF proteins into nucleus. We investigated the critical factors that facilitate the nuclear transport of triple C2H2 ZF proteins. Three conserved basic residues (hot spots) were identified among the ZF sequences of triple C2H2 ZF proteins that reportedly have NLS function. Additional basic residues can be found on the α-helix of the ZFs. Using the ZF domain (ZFD) of Egr-1 as a template, various mutants were constructed and expressed in cells. The nuclear transport activity of various mutants was estimated by analyzing the proportion of protein localized in the nucleus. Mutation at any hot spot of the Egr-1 ZFs reduced the nuclear transport activity. Changes of the basic residues at the α-helical region of the second ZF (ZF2) of the Egr-1 ZFD abolished the NLS activity. However, this activity can be restored by substituting the acidic residues at the homologous positions of ZF1 or ZF3 with basic residues. The restored activity dropped again when the hot spots at ZF1 or the basic residues in the α-helix of ZF3 were mutated. The variations in nuclear transport activity are linked directly to the binding activity of the ZF proteins with importins. This study was extended to other triple C2H2 ZF proteins. SP1 and KLF families, similar to Egr-1, have charged amino acid residues at the second (α2) and the third (α3) positions of the α-helix. Replacing the amino acids at α2 and α3 with acidic residues reduced the NLS activity of the SP1 and KLF6 ZFD. The reduced activity can be restored by substituting the α3 with histidine at any SP1 and KLF6 ZFD. The results show again the interchangeable role of ZFs and charge residues in the α-helix in regulating the NLS activity of triple C2H2 ZF proteins.

Polyunsaturated fatty acids and inflammatory markers in major depressive episodes during pregnancy.

INTRODUCTION: Prenatal depression (PND) is a common psychiatric disorder in pregnant women and leads to psychosocial dysfunction, high suicidal rate, and adverse childcare. Patients with PND have omega-3 polyunsaturated fatty acid (omega-3 or n-3 PUFAs) deficits, which might link to chronic low-grade inflammatory process and the pathophysiological mechanisms of depression. In this case-control study, we examined the levels of PUFAs and inflammatory cytokines in PND. METHOD: Blood samples were obtained and analyzed from 16 healthy controls and 17 depressed cases (PND group) diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Independent sample t-test and correlation analysis were performed with Statistical Package for the Social Sciences (SPSS) logistics correlation analysis. RESULTS: PND group had significantly lower levels of total n-3 (p=0.026), docosahexaenoic acid (DHA) (p=0.020) and eicosapentaenoic (EPA) (p=0.019) but a higher omega-6 (n-6)/n-3 PUFAs ratio (p=0.007) and tumor necrosis factor alpha (TNF-α) (p=0.016) level. Moreover, the duration of current PND episodes were also significantly correlated with DHA, EPA, n-3 PUFAs, n-6/n-3 ratio and TNF-α. In terms of PUFAs and cytokine levels, only DHA was inversely correlated with TNF-α. CONCLUSION: PND is significantly associated with lower DHA, EPA, and total n-3 PUFAs levels and an increased n-6/n-3 PUFAs ratio, while the duration of PND is associated with lower levels of n-3 PUFAs, including DHA and EPA. The correlation of PUFAs levels with depression and TNF-α level grant further investigation into the inflammatory process underlying PND, mediated by PUFAs.