EGR3 Polymorphism Is a Potential Susceptibility Factor of Schizophrenia Risk in a Chinese Population.

Objective: The purpose of this study was to evaluate the association between the single nucleotide polymorphisms (SNPs) (EGR3 rs1996147; EGR4 rs3813226, rs6747506; ERBB3 rs2292238; and ERBB4 rs707284, rs7560730) and the risk of schizophrenia (SZ) in a Chinese population. Materials and Methods: We conducted a case-control study, including 248 patients with SZ and 236 healthy controls matched for age and sex. The Mass-array platform was used to detect all the genotypes of the SNPs. Results: The results revealed that the EGR3 rs1996147 AA genotype was associated with borderline decreased SZ risk (AA vs. GG: adjusted OR = 0.43, 95% CI: 0.18-1.02, p = 0.06). However, no significant correlation was found between the other SNPs and overall SZ risk. Subgroup analysis also failed to show any significant association between all SNPs and the risk of SZ. Conclusion: In summary, this study revealed that the EGR3 rs1996147 AA genotype was associated with a borderline risk for SZ.

Association Between Polymorphisms in DNA Damage Repair Pathway Genes and Female Breast Cancer Risk.

Breast cancer risk have been discussed to be associated with polymorphisms in genes as well as abnormal DNA damage repair function. This study aims to assess the relationship between genes single nucleotide polymorphisms (SNPs) related to DNA damage repair and female breast cancer risk in Chinese population. A case-control study containing 400 patients and 400 healthy controls was conducted. Genotype was identified using the sequence MassARRAY method and expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) in tumor tissues was analyzed by immunohistochemistry assay. The results revealed that ATR rs13091637 decreased breast cancer risk influenced by ER, PR (CT/TT vs. CC: adjusted odds ratio [OR] = 1.54, 95% confidence interval [CI]: 1.04-2.27, p = 0.032; CT/TT vs. CC: adjusted OR = 1.63, 95%CI: 1.14-2.35, p = 0.008) expression. Stratified analysis revealed that PALB2 rs16940342 increased breast cancer risk in response to menstrual status (AG/GG vs. AA: adjusted OR = 1.72, 95%CI: 1.13-2.62, p = 0.011) and age of menarche (AG/GG vs. AA: adjusted OR = 1.54, 95%CI: 1.03-2.31, p = 0.037), whereas ATM rs611646 and Ku70 rs132793 were associated with reduced breast cancer risk influenced by menarche (GA/AA vs. GG: adjusted OR = 0.50, 95%CI: 0.30-0.95, p = 0.033). In a summary, PALB2 rs16940342, ATR rs13091637, ATM rs611646, and Ku70 rs132793 were associated with breast cancer risk.

Association between atherogenic index of plasma and prehypertension or hypertension among normoglycemia subjects in a Japan population: a cross-sectional study.

OBJECTIVE: The atherogenic index of plasma (AIP), consisting of triglycerides and high-density lipoprotein cholesterol, is applied to estimate the cardiovascular disease risk. The evidence regarding the association between AIP and prehypertension or hypertension remains inconclusive. This study was conducted to investigate the association of AIP and prehypertension or hypertension in normoglycemic subjects in Japan. METHODS: In the present cross-sectional study, 15,453 normoglycemic participants aged 18 years or older in Gifu, Japan, were evaluated. The selected participants were separated into four groups in the light of AIP quartiles, ranging from the lowest quartile (Q1) to the highest quartile (Q4). And the association between AIP and prehypertension or hypertension was explored with multivariate logistic regression by gradually adjusting model. RESULTS: Among the 15,453 participants, aged of 43.7 ± 8.9 years, and of whom 45.5% were females, the prevalence rates of prehypertension or hypertension were 27.68% (4,278) and 6.23% (962) respectively. In multivariate logistic regression analyses, participants in the highest AIP quartile had an increase risk in prehypertension and hypertension, compared with participants the lowest one, the odds ratios (OR) were 1.15 (95%CI: 1.00-1.13, P = 0.045) for prehypertension and 1.54 (95%CI:1.16-2.04, P = 0.003) for hypertension after adjusting confounders. In subgroup analyses, the high risk of hypertension was also observed for female participants in the highest AIP quartile (Q4) (OR = 2.19, 95%CI: 1.37-3.49, P = 0.001), especially between the ages of 40 and 60 years (OR = 2.20, 95%CI: 1.24-3.88, P = 0.007). CONCLUSIONS: Higher AIP is significantly and positively associated with the risk of prehypertension or hypertension in normoglycemic subjects in Gifu, Japan, which was more pronounced in the female population, especially between the years of 40 and 60.

Global monkeypox outbreak 2022: First case series in Singapore.

Monkeypox is a global health emergency. Prior to 2022, there were few reports of monkeypox outside of endemic countries, which were mostly travel-related. Since May 2022, an exponential increase in monkeypox infections in previously non-endemic countries has been reported. Unlike previous outbreaks of monkeypox, which were zoonotically transmitted and presented with generalised vesicular eruptions after prodromal symptoms, cases of the current outbreak feature significant travel and sexual history, and atypical localised genital eruptions with unpredictable onset relative to viral prodrome-like symptoms. We summarise the 15 Singapore cases reported to date as of August 2022, and highlight salient clinical clues that may aid physicians in narrowing the broad differential diagnosis of an acute vesicular genital eruption. Although research into vaccination and antiviral strategies is ongoing, monkeypox is currently conservatively managed. Clinical vigilance and a high index of suspicion are required to facilitate early detection and isolation of cases to contain transmission in Singapore.

Circular RNA Rbms1 inhibited the development of myocardial ischemia reperfusion injury by regulating miR-92a/BCL2L11 signaling pathway.

Acute myocardial infarction (AMI) is characterized by high morbidity and mortality rates. Circular RNAs collectively participate in the initiation and development of AMI. The purpose of this study was to investigate the role of circRbms1 in AMI. Ischemia-reperfusion (I/R) was performed to establish an AMI model. RT-qPCR and Western blotting were performed to detect mRNA and analyze protein expression, respectively. The interaction between miR-92a and circRbms1/BCL2L11 was confirmed by luciferase and RNA pull-down assays. circRbms1 is overexpressed in AMI. However, circRbms1 knockdown alleviated H9c2 cell apoptosis and reduced the release of reactive oxygen species. circRbms1 targeted miR-92a, the downregulation of which alleviated the effects of circRbms1 knockdown and increased oxidative stress and H9c2 cell apoptosis. Moreover, circRbms1 sponged miR-92a to upregulate BCL2L11, which modulated the expression of apoptosis-related genes. circRbms1 participated in myocardial I/R injury by regulating the miR-92a/BCL2L11 signaling pathway, which may provide a new strategy for the treatment of AMI.

Estimating the proportion of people with chronic hepatitis B virus infection eligible for hepatitis B antiviral treatment worldwide: a systematic review and meta-analysis.

BACKGROUND: In 2016, of the estimated 257 million people living with chronic hepatitis B virus (HBV) infection worldwide, only a small proportion was diagnosed and treated. The insufficiency of information on the proportion of people infected with HBV who are eligible for treatment limits the interpretation of global treatment coverage. We aimed to estimate the proportion of people with chronic HBV infection who were eligible for antiviral treatment worldwide, based on the WHO 2015 guidelines. METHODS: In this systematic review and meta-analysis, we searched Medline, EMBASE, and the Cochrane databases from Jan 1, 2007, to Jan 31, 2018, for studies describing HBsAg-positive people in the population or health-care facilities. We extracted information from published studies using a standardised form to estimate the frequency of cirrhosis, abnormal alanine aminotransferase (ALT), HBV DNA exceeding 2000 IU/mL or 20 000 IU/mL, presence of HBeAg, and eligibility for treatment as per WHO and other guidelines as reported in the studies. We pooled proportions through meta-analysis with random effects. The study was registered with PROSPERO, CRD42020132345. FINDINGS: Of the 13 497 studies, 162 were eligible and included in our analysis. These studies included 145 789 participants. The pooled estimate of the proportion of cirrhosis was 9% (95% CI 8-10), ranging from 6% (4-8) in community settings to 10% (9-11) in clinic settings. Examining the proportion of participants who had characteristics used to determine eligibility in the WHO guidelines, 1750 (10·1%) of 17 394 had HBV DNA exceeding 20 000 IU/mL, and 20 425 (30·8%) of 66 235 had ALT above the upper limit of normal. 32 studies reported eligibility for treatment according to WHO or any other guidelines, with a pooled estimate of eligibility at 19% (95% CI 18-20), ranging from 12% (6-18) for studies in community settings to 25% (19-30) in clinic settings. INTERPRETATION: Many studies described people with HBV infection, but few reported information in a way that allowed assessment of eligibility for treatment. Although about one in ten of the 257 million people with HBV infection (26 million) might be in urgent need of treatment because of cirrhosis, a larger proportion (12-25%) is eligible for treatment in accordance with different guidelines. Future studies describing people with HBV infection should report on treatment eligibility, according to broadly agreed definitions. FUNDING: WHO and US Centers for Disease Control and Prevention.

Association between Free Thyroxine Levels and Diabetic Retinopathy in Euthyroid Patients with Type 2 Diabetes Mellitus.

Background: This study aimed to evaluate the association between thyroid parameters and diabetic retinopathy (DR) in euthyroid patients with type 2 diabetes mellitus (T2DM).Materials and Methods: In this cross-sectional study, a total of 911 euthyroid patients with T2DM (539 men and 372 women; mean age, 60.81 ± 12.93 years) were enrolled. Clinical factors were assessed and free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels were measured. DR was diagnosed using fundus fluorescein angiography.Results: Compared with patients without DR (n = 718), patients with DR (n = 193) exhibited lower FT3 (4.40 ± 0.58 vs. 4.50 ± 0.51 pmol/L; P = .019) and FT4 (14.86 ± 2.09 vs. 15.91 ± 2.18 pmol/L; P < .001) and higher TSH (1.86 [1.22, 2.66] vs. 1.58 [1.14, 2.34] µIU/mL; P = .015) levels. After adjustment for potential DR risk factors, patients in the highest tertile of plasma FT4 levels had a 0.332-fold likelihood of developing DR compared with those in the lowest tertile of plasma FT4 levels (Ptrend < 0.001). The prevalence of DR showed a significantly decreasing trend across the three tertiles based on FT4 levels (31.35%, 19.08% and 13.16%; Ptrend < 0.001). Similar results were obtained for the presence of proliferative DR.Conclusion: These findings suggest that low-normal FT4 levels are associated with the prevalence of DR in euthyroid patients with T2DM.

Association between thyroid function and diabetic nephropathy in euthyroid subjects with type 2 diabetes mellitus: a cross-sectional study in China.

Previous studies have suggested that even in euthyroid subjects, thyroid function may affect the risk factors of diabetic nephropathy (DN). Thus, we investigated the association between thyroid parameters and DN in euthyroid subjects with type 2 diabetes mellitus (T2DM). This was a cross-sectional study of 1,071 euthyroid subjects with T2DM (mean age of 61.90 ± 12.74 years; 622 men). Clinical factors, including levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroid autoantibodies, albumin excretion rate were measured. DN was present in 400 (37.35%) individuals. Patients with DN exhibited higher serum TSH and lower serum FT3 and FT4 levels than those without DN (P<0.05). After adjusting traditional risk factors of DN, the levels of both FT3 (per-SD increase, odds ratio [OR] 0.606 [95% confidence interval (CI), 0.481-0.762], P<0.001) and FT4 (per-SD increase, OR 0.944 [0.894-0.998], P = 0.040) were inversely correlated with DN. Meanwhile, we found that serum TSH levels were positively correlated with DN (per-SD increase, OR1.179 [1.033-1.346], P = 0.015). Low-to-normal thyroid hormones (THs) were also associated with the presence of macroalbuminuria. In conclusion, the relatively low levels of THs were significantly associated with DN in euthyroid subjects with T2DM.

Paravertebral Block for Inguinal Herniorrhaphy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Paravertebral block (PVB) is a safe and effective anesthetic technique for thoracotomy and mastectomy. However, no systematic review or meta-analysis has focused on PVB for inguinal herniorrhaphy. Our study compares PVB with general anesthesia/systemic analgesia, neuraxial blocks, and other peripheral nerve blocks. METHODS: We analyzed 14 randomized controlled trials from PubMed, MEDLINE, CENTRAL, EMBASE, and CINAHL up to February 2015, without language restriction, comparing PVB under sedation with general anesthesia/systematic analgesia (135 vs 133 patients), neuraxial blocks (191 vs 186 patients), and other peripheral nerve blocks (119 vs 117 patients). We investigated pain scores, consumption of postoperative analgesia, incidence of postoperative nausea and vomiting (PONV), length of hospital stay, postanesthesia care unit bypassing rate, time to perform blocks, intraoperative hemodynamics, and incidence of urinary retention. Joint hypothesis testing was adopted for pain and analgesics, PONV, and hemodynamic variables. All analyses were performed with RevMan 5.2.11 (Cochrane Collaboration, Copenhagen). Hartung-Knapp-Sidik-Jonkman method was used for post hoc testing. RESULTS: PVB reduced PONV (nausea: risk ratio [RR] = 0.22; 95% confidence interval [CI], 0.05-0.93; numbers needed to treat [NNT] = 4.5; I = 15% and vomiting: RR = 0.15; 95% CI, 0.03-0.76; NNT = 8.3; I = 0%) compared with general anesthesia/systematic analgesia (quality of evidence [QoE]: high). Compared with neuraxial blocks, PVB resulted in less postoperative nausea (RR = 0.34 [95% CI, 0.13-0.91], NNT = 8.3, I = 0%) and urinary retention (RR = 0.14 [95% CI, 0.05-0.42], NNT = 7.4, I = 0%) than neuraxial blocks (QoE: high). More time was needed to perform PVB than neuraxial blocks (standardized mean difference = 1.90 [95% CI, 0.02-3.77], I = 92%; mean difference = 5.33 minutes; QoE: moderate). However, the available data could not reject the null hypothesis of noninferiority on all pain scores and analgesic requirements for both PVB versus general anesthesia/systematic analgesia and PVB versus neuraxial blocks (QoE: low), as well as on hemodynamic outcomes for PVB versus neuraxial blocks (QoE: moderate). Our systematic review showed that PVB decreased postoperative pain scores and analgesic requirement as compared with ilioinguinal block and transversus abdominis plane block. CONCLUSIONS: This meta-analysis shows that PVB provides an anesthesia with fewer undesirable effects for inguinal herniorrhaphy. The choice between general anesthesia/systematic analgesia, neuraxial blocks, PVB, and other peripheral nerve blocks should be based on time available to perform the block and a complete coverage over the relevant structures by the blocks.

Lidocaine patch for acute pain management: a meta-analysis of prospective controlled trials.

BACKGROUND: Local anesthetic is one of the cornerstones of multimodal analgesia. We investigated the efficacy of the lidocaine patch for acute pain management. METHODS: We searched MEDLINE, CINAHL, Scopus, and the Cochrane Controlled Trials Register for published prospective controlled clinical trials that evaluated the analgesic effect of the lidocaine patch for acute or postoperative pain management (1966--2014). The outcomes were postoperative opioid consumption, pain intensity and length of hospital stay. RESULTS: Five trials comparing the lidocaine patch with control (no treatment/placebo) for acute or postoperative pain treatment/management were included in this meta-analysis. Data was analyzed on 251 patients. Between the lidocaine patch group and the control group, no significant difference was found for all three outcomes (all p > 0.05). For postoperative opioid consumption, mean difference (MD) was -8.2 mg morphine equivalent (95% CI -28.68, 12.24). For postoperative pain intensity, MD was -9.1 mm visual analog scale or equivalent (95% CI -23.31, 5.20). For length of hospital stay, MD was -0.2 days (95% CI -0.80, 0.43). CONCLUSION: Application of a lidocaine patch may not be an effective adjunct for acute and postoperative pain management, in terms of pain intensity, opioid consumption and length of hospital stay. LIMITATIONS: The limitations were a small number of included studies, potential biases from some unblinded studies, clinical heterogeneity between studies, and incomplete reported data for adjunct analgesics.

Optimizing pain management to facilitate Enhanced Recovery After Surgery pathways.

PURPOSE: The optimal management of postoperative pain using multimodal analgesia is a key component of Enhanced Recovery After Surgery (ERAS). Pain has adverse clinical implications on postoperative recovery, including prolonging the time to recovery milestones and length of hospital stay. Moreover, the ubiquity of opioids in postoperative analgesic regimens results in adverse effects, such as sedation, postoperative nausea and vomiting, urinary retention, ileus, and respiratory depression, which can delay discharge. Thus, multimodal analgesia, i.e., the use of more than one analgesic modality to achieve effective pain control while reducing opioid-related side effects, has become the cornerstone of enhanced recovery. The purpose of this review is to address the analgesic techniques used as part of multimodal analgesic regimens to optimize postoperative pain control and to summarize the evidence for their use in reducing opioid requirements and side effects. PRINCIPAL FINDINGS: There is a wide variety of analgesic techniques available for multimodal postoperative analgesia. These modalities are divided into pharmacological and non-pharmacological techniques. Systemic pharmacological modalities involve opioids and non-opioids such as acetaminophen, non-steroidal anti-inflammatory drugs, N-methyl-D-aspartate receptor antagonists, anticonvulsants (e.g., gamma-aminobutyric acid analogues), beta-blockers, alpha-2 agonists, transient receptor potential vanilloid receptor agonists (capsaicin), and glucocorticoids. Other pharmacological modalities include central neuraxial techniques, surgical-site infiltration, and regional anesthesia. Evidence supports the use of these pharmacological techniques as part of multimodal analgesia, but each has its own advantages and specific safety profile, which highlights the importance of selecting the appropriate analgesics for each patient. Adjunctive non-pharmacological techniques include acupuncture, music therapy, transcutaneous electrical nerve stimulation, and hypnosis. There is mixed evidence regarding such techniques, although a lack of harm is associated with their use. CONCLUSION: There are continuing advancements in multimodal analgesic techniques; however, postoperative pain in general continues to be undermanaged. Furthermore, a continuing challenge in multimodal pain research related to ERAS is the difficulty in carrying out randomized trials to determine the relative importance of any one component, including analgesia.

[Suppressive effect of induced CD4+CD25+ regulatory T cells from mice infected with Schistosoma japonicum].

OBJECTIVE: To investigate the suppressive effect of CD4+CD25+ regulatory T cells from mice infected with Schistosoma japonicum. METHODS: BALB/c mice were infected with S. japonicum. At 6 and 13 weeks post-infection, the spleens were removed and CD4+CD25+ T cells were separated by magnetic beads. In in vitro experiments, CD4+CD25+ T Cells were cocultured with CD4+CD25- T cells. The inhibitory role of the CD4+CD25+ T cells was assessed by [3H] thymidine incorporation method and the cytokines in the cultural supernatant were detected by ELISA. In in vivo experiments, mice inoculated with irradiated cercariae of S. japonicum were adoptively transferred with CD4+CD25+ T cells isolated from the mice chronically infected with S. japonicum. The intracellular cytokine expressions of splenocytes were performed by flow cytometry, and sera IgG1 and IgG2a antibodies against irradiated cercaria antigens were detected by ELISA. RESULTS: In vitro, CD4+CD25+ T cells were able to suppress the proliferation of CD4+CD25- T cells when stimulated with SEA, compared with single CD4+CD25- T cells culture (cpm 7615 +/- 1 058) (P < 0.01). Furthermore, CD4+CD25+ T cells isolated from mice chronically infected with S. japonicum presented higher suppressive efficacy (cpm 2 336 +/- 490), compared with that isolated from the acutely infected mice (cmp 4 467 +/- 144) (P < 0.05). Meanwhile, CD4+CD25+ T cells isolated from mice with the acute infection inhibited the cytokine secretion by CD4+CD25- T cells and the suppression rate was 32.0% for IL-4 (P < 0.05), 66.3% for IFN-gamma (P < 0.01) and 63.2% for IL-2 (P < 0.01), respectively, and CD4+CD25+ T cells isolated from mice with the chronic infection, the suppression rate was 28.4% for IL-4 (P < 0.05), 60.1% for IFN-gamma (P < 0.01) and 58.3% for IL-2 (P < 0.01), respectively. In vivo, IFN-gamma secretion and IgG2a antibody production of mice adoptively transferred with CD4+CD25+ T cells from the chronically infected mice were suppressed when mice were inoculated with irradiated cercariae of S. japonicum (P < 0.05). CONCLUSION: CD4+CD25+ T cells isolated from mice infected with S. japonicum have played roles of Th1-dominant immune suppression.

[Changes of CD4+CD25+ T cells in the spleen of mice infected with Toxoplasma gondii].

OBJECTIVE: To observe the changes of CD4+CD25+ regulatory T cells in the spleen of mice infected with T.gondii. METHODS: Twenty-eight female C57BL/6 mice were randomly divided into four groups. Three groups of mice were inoculated intraperitoneally with 10(4) tachyzoites in 200 microl sterile PBS. At 2, 4 and 6 days post-infection, the spleens were removed. The expression level of Foxp3 mRNA in splenic CD4+ T cells was quantitated by real-time PCR. The percentage of CD4+CD25+ regulatory T cells in CD4+ T cells was determined by flow cytometry, and the absolute numbers of splenic CD4+CD25 - regulatory T cells and CD4+ T cells were assessed. The fourth group was injected intraperitoneally with 200 microl sterile PBS as control. RESULTS: The relative mRNA level of Foxp3 in splenic CD4+ T cells at day 4 (1.89+/-0.23) and day 6 (1.79+/-0.24) post-infection was significantly higher than control (1.00+/-0.12) (P< 0.01). After an initial up-regulation at 2 days post-infection (15.07%+/-2.73%) (P<0.05), the proportion of CD4+CD25+ regulatory T cells in CD4+ T cells at day 4 (24.29%+/-3.19%) and day 6 (19.80%+/-2.66%) post-infection was significantly higher than control (11.58%+/-2.04%) (P<0.01). At day 6 post-infection, both the percentage of splenic CD4+ T cells in splenocytes(5.49%+/-l.71%) and absolute number of CD4+ T cells (1.71+/-0.44)x106 greatly decreased(P<0.01). CONCLUSION: The proportion of splenic CD4+CD25+ regulatory T cells in CD4+ T cells has been up-regulated following T. gondii infection, which is mainly due to a great reduction of CD4+ T cells in the spleen.