Hypoxia-responsive Immunostimulatory Nanomedicines Synergize with Checkpoint Blockade Immunotherapy for Potentiating Cancer Immunotherapy.

Inducing cell death while simultaneously enhancing antitumor immune responses is a promising therapeutic approach for multiple cancers. Celastrol (Cel) and 7-ethyl-10-hydroxycamptothecin (SN38) have contrasting physicochemical properties, but strong synergy in immunogenic cell death induction and anticancer activity. Herein, a hypoxia-sensitive nanosystem (CS@TAP) was designed to demonstrate effective immunotherapy for colorectal cancer by systemic delivery of an immunostimulatory chemotherapy combination. Furthermore, the combination of CS@TAP with anti-PD-L1 mAb (αPD-L1) exhibited a significant therapeutic benefit of delaying tumor growth and increased local doses of immunogenic signaling and T-cell infiltration, ultimately extending survival. We conclude that CS@TAP is an effective inducer of immunogenic cell death (ICD) in cancer immunotherapy. Therefore, this study provides an encouraging strategy to synergistically induce immunogenic cell death to enhance tumor cytotoxic T lymphocytes (CTLs) infiltration for anticancer immunotherapy.

Retracted: The Clinical Effectiveness of Calcium Hydroxide in Root Canal Disinfection of Primary Teeth: A Meta-Analysis.

This publication has been retracted by the Editor due to non-original content and deficiencies in the conduct of the study. Reference: Liying Jia, Xiaolin Zhang, Hong Shi, Ting Li, Bingjian Lv, Meng Xie. The Clinical Effectiveness of Calcium Hydroxide in Root Canal Disinfection of Primary Teeth: A Meta-Analysis. Med Sci Monit, 2019; 25: 2908-216. DOI: 10.12659/MSM.913256.

Relationship between preterm, low birth weight, and development defects of enamel in the primary dentition: A meta-analysis.

Background: This study aimed to systematically analyze the relationship between preterm (PT), low birth weight (LBW), and developmental defects of enamel (DDE) in the primary dentition. Methods: Following the retrieval of the databases, case-control studies, cross-sectional studies, and cohort studies on the relationship between PT, LBW and DDE, which had been published in English or Chinese up to January 2022 were included. The data about odds ratio (OR) and 95% confidence interval (95% CI) were extracted and calculated using STATA 12.0 Software. Case-control studies were evaluated using the Newcastle-Ottawa Scale (NOS), while cross-sectional studies and cohort studies were evaluated using the JBI scale. The heterogeneity of each study was evaluated using the Q test. Results: A total of 15 studies were included, of which 8 studied the relationship between PT and DDE, and 13 explored the relationship between LBW and DDE including three about the relationship between very low birth weight (VLBW) and DDE. Seven studies explored the relationship between PT, LBW, and DDE. The results of this meta-analysis showed that both PT and LBW especially VLBW (OR = 7.19, 95% CI: 4.98-10.38) were risk factors for DDE in the primary dentition (OR = 2.33, 95% CI: 1.55-3.51) (OR = 1.67, 95% CI: 1.08-2.59). The subgroup results showed that PT and LBW were both associated with the occurrence of enamel hypoplasia (EHP) (OR = 6.89, 95% CI: 3.33-14.34; OR = 2.78, 95% CI: 2.10-3.68) rather than enamel opacity (OR = 0.94, 95% CI: 0.55-1.61; OR = 1.03, 95% CI: 0.66-1.61). There was no publication bias about the included studies (P = 0.75 > 0.05; P = 0.47 > 0.05). Conclusion: This meta-analysis demonstrated that both PT and LBW especially VLBW are associated with a higher risk of DDE in the primary dentition. PT and LBW are both related to the occurrence of EHP. However, the relationship between PT, LBW, and enamel opacity has not been verified. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier: CRD42021262761.

Muscone suppresses myocardial ischemia damage by regulating PI3K/Akt signaling pathway.

Muscone is the main active compound of Moschus. In this paper, the cardioprotective effect of Muscone on acute myocardial ischemia (AMI) rats and its potential mechanisms were investigated. AMI rat models were established to evaluate the protective effect and antioxidative function of Muscone on the hearts. Moreover, Western blot analysis was conducted to quantify the phosphorylated PI3K and AKT levels in PI3K/Akt pathway for further investigating the mechanism of Muscone. Results showed that Muscone could markedly lessen the infarct size and myocardial injury, improve cardiac function, inhibit cardiomyocyte apoptosis and down-regulate serum reactive oxygen species level as indicated by the decreased MDA, BNP and c-TnI activities and the increased SOD, GSH-px, CAT activities and the expression of Bax protein. In addition, it was revealed that Muscone notably promoted the phosphorylation of PI3K and AKT. These findings denote that Muscone exerts a protective effect in heart via inhibition of oxidative stress and apoptosis, offering new insights into the treatment of CHD and the clinical application of Muscone.

Cardioprotective Effects of Tetrahydropalmatine on Acute Myocardial Infarction in Rats.

Tetrahydropalmatine (THP) is an active component of Corydalis yanhusuo W. T. Wang. The current study investigates the possible cardioprotective effects of tetrahydropalmatine in acute myocardial ischemia (AMI) rats. The anterior descending coronary artery of SD rats was ligated to establish an AMI model. After two weeks of gavage of THP, cardiac function was determined by echocardiography. The organ index and the infarct size were assessed after the experiment, and the histopathological myocardial tissue changes were observed. In addition, the apoptosis index of myocardial cells was detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The levels of SOD, MDA, CAT, GSH-Px, BNP, and cTn-I were measured by enzyme-linked immunosorbent assay. To determine relevant proteins, the Western blot and molecular docking were applied. Compared with the model group, THP could enhance rat cardiac ejection function to improve cardiac function, drastically lessen the infarct size, reduce myocardial cell damage and inflammatory cell infiltration. THP might also prevent ischemic myocardial damage by inhibiting myocardial cell apoptosis and efficiently reducing oxidative stress. Specifically, THP could decrease MDA, BNP, c-TnI activities, as well as the expression of Bax and Caspase-3 protein, while increasing SOD, GSH-Px, CAT activities, and Bcl-2 level. Furthermore, THP could significantly promote the phosphorylation of PI3K and Akt proteins. The involved pathways and proteins have also been verified through molecular docking. According to these findings, THP may preserve the myocardium due to its anti-oxidant and anti-apoptotic properties.

Probing depth reduction of laser application in periodontal therapy: a network meta-analysis.

The aim was to systematically evaluate the probing depth (PD) reduction of lasers in scaling and root planing (SRP) of chronic periodontitis by network meta-analysis (NMA). Randomized controlled clinical trials (RCTs) were searched through electronic-search and hand-search up to January 2020. Standard mean different (SMD) and 95% confidence interval (CI) were counted for PD reduction. The random-effects NMA were performed using mvmeta routine in STATA software (version 13). This NMA analysed seven periodontal treatments through 37 RCTs. No inconsistency was detected. Compared with mechanical SRP, significant differences were in favour of diode laser (DL) as adjunct at 3 months (SMD = 0.61; 95% CI range: 0.27-0.96) and Nd:YAG as adjunct (SMD = 0.29; 95% CI range: 0.03-0.55), Er,Cr:YSGG as monotherapy (SMD = 0.37; 95% CI range: 0.04-0.71) and Er,Cr:YSGG as adjunct (SMD = 0.53; 95% CI range: 0.23-0.84) at 6 months after treatment. Compared with Er:YAG as monotherapy, significant differences were in favour of DL as adjunct at 6 months (SMD = 0.51; 95% CI range: 0.07-0.95) after treatment. In terms of PD reduction at 3-month follow-up, the ranking result from best to worst was Nd:YAG as adjunct, DL as adjunct, Er:YAG as adjunct, Er,Cr:YSGG as monotherapy, Er:YAG as monotherapy and mechanical SRP. In terms of PD reduction at 6-month follow-up, the ranking result was DL as adjunct, Nd:YAG as adjunct, Er:YAG as adjunct, Er,Cr:YSGG as adjunct, Er:YAG as monotherapy, Er,Cr:YSGG as monotherapy and mechanical SRP. Laser-assisted periodontal treatment has better PD reduction.

Investigating the Pharmacological Mechanisms of SheXiang XinTongNing Against Coronary Heart Disease Based on Network Pharmacology and Experimental Evaluation.

SheXiang XinTongNing (XTN), which is composed of six traditional Chinese herbs, is a commercially available Chinese patent medicine that has been widely used as the treatment of coronary heart disease (CHD). Its mechanisms against coronary heart disease, however, remain largely unknown. This study aimed to investigate the pharmacological mechanisms of XTN against CHD via network pharmacology and experimental evaluation. In this study, GO enrichment and KEGG pathway enrichment were firstly performed for acquiring the potentially active constituents of XTN, the candidate targets related to coronary heart disease, the drug-components-targets network as well as the protein-protein interaction network and further predicting the mechanisms of XTN against coronary heart disease. Subsequently, a series of in vitro experiments, specifically MTT assay, flow cytometry and Real-time quantitative polymerase chain reaction analysis, and a succession of in vivo experiments, including Tunel staining and immunohistochemical staining were conducted for further verification. Results showed that Bcl-2, IGF1, CASP3 were the key candidate targets which significantly associated with multiple pathways, namely PI3K-Akt signaling pathway and MAPK signaling pathway. It indicated that the potential mechanism of XTN against CHD may be predominantly associated with cell apoptosis. The in vitro experimental results showed that XTN treatment remarkably decreased the apoptotic rate and Bax/Bcl-2 ratio of H9c2 cells. Histological results confirmed that XTN not only effectively alleviated oxidative damage caused by myocardial ischemia but inhibited cell apoptosis. Given the above, through the combined utilization of virtual screening and experimental verification, the findings suggest that XTN makes a significant contribution in protecting the heart from oxidative stress via regulating apoptosis pathways, which lays the foundations and offers an innovative idea for future research.

Screen of anti-migraine active compounds from Duijinsan by spectrum-effect relationship analysis and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Duijinsan (DJS) is a famous Chinese medicine prescription composed of Radix scutellariae (RS) and Rhei Radix (RRR), which has been mainly used for treating migraine. AIM OF THE STUDY: This study aimed to uncover the anti-migraine active compounds from DJS and preliminary predicted the pharmacological mechanism by evaluating the spectrum-effect relationship between high-performance liquid chromatography (HPLC) fingerprints and anti-migraine effects of Duijinsan (DJS) extract combined with molecular docking. MATERIALS AND METHODS: HPLC and LC-MS were applied for chemical analyses of DJS extracts in different proportions. Inhibition of DJS extracts on trigeminal nerve cell releasing calcitonin gene related peptide (CGRP) experiment was performed. The active compounds were screened by spectrum-effect relationship analysis and confirmed by molecular docking and the activities of major predicted compounds were validated in vitro. RESULTS: Twenty-six common peaks were assigned and identified from the fingerprints of different proportions DJS extracts. In vitro experimental results showed that DJS extracts inhibited inflammation and release of CGRP from trigeminal nerve cells. Five predicted active compounds, Chrysin 6-C-arabinoside 8-C-glucoside, Chrysin 6-C-glucoside 8-C-arabinoside, baicalin, Chrysin-7-O-Beta-D-glucoronide and Oroxylin A 7-O-glucuronide were sorted out according to spectrum-effect relationship analysis and molecular docking comprehensively. In vitro validation experiments showed that all the predicted compounds inhibited the CGRP releasing and the activation of TRPV1 channel. Baicalin, chrysin-7-O-ß-D-glucuronide and Oroxylin A-7-glucoronide significantly inhibited the activation of TRPV1 channel. CONCLUSION: Chrysin 6-C-arabinoside 8-C-glucoside, Chrysin 6-C-glucoside 8-C-arabinoside, baicalin, Chrysin-7-O-Beta-D-glucoronide and Oroxylin A 7-O-glucuronide which can inhibit the CGRP releasing and the activation of TRPV1 channel were screened as the anti-migraine active compounds by spectrum-effect relationship analysis and molecular docking.

The Effectiveness of Photobiomodulation on Accelerating Tooth Movement in Orthodontics: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis evaluated the effectiveness of photobiomodulation therapy (PBMT) on accelerating orthodontic tooth movement (OTM) in clinical practice. Methods: Data from bilingual journals across seven different databases were compiled and analyzed. Randomized controlled trials (RCTs) and quasi-RCTs regarding the effect of PBMT on OTM in cases with four first premolar extractions in split-mouth design were selected. This study was conducted after approval from the IRB. The outcome variables were the cumulative tooth movement distances in 1, 2, and 3 months. Data extraction was performed by two authors independently and in duplicate. Risk of bias was assessed. Results: Eight RCTs and one quasi-RCT were ultimately included and analyzed in meta-analysis. This study revealed that the pooled mean difference (MD) among these trials was 0.30 [95% confidence interval (CI): -0.02 to 0.62], 0.69 (95% CI: 0.08 to 1.29), and 0.64 (95% CI: -0.01 to 1.29) for 1, 2, and 3 months, respectively. The results remained consistent after sensitivity analysis assessment. Conclusions: There is insufficient evidence to support that photobiomodulation accelerates tooth movement in orthodontic treatments. Our results suggest that the optimal parameters of PBMT on OTM in human might be about 20 mW, 5-8 J/cm2, 0.5 W/cm2, 0.2 J/point, and 2-10 J/tooth. More large-sample multicenter clinical trials carried out in similar settings are required to confirm and pinpoint treatment efficiency and optimal parameters. Registration: The review protocol was not registered prior to the study.

Payment methods for healthcare providers working in outpatient healthcare settings.

BACKGROUND: Changes to the method of payment for healthcare providers, including pay-for-performance schemes, are increasingly being used by governments, health insurers, and employers to help align financial incentives with health system goals. In this review we focused on changes to the method and level of payment for all types of healthcare providers in outpatient healthcare settings. Outpatient healthcare settings, broadly defined as 'out of hospital' care including primary care, are important for health systems in reducing the use of more expensive hospital services. OBJECTIVES: To assess the impact of different payment methods for healthcare providers working in outpatient healthcare settings on the quantity and quality of health service provision, patient outcomes, healthcare provider outcomes, cost of service provision, and adverse effects. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase (searched 5 March 2019), and several other databases. In addition, we searched clinical trials platforms, grey literature, screened reference lists of included studies, did a cited reference search for included studies, and contacted study authors to identify additional studies. We screened records from an updated search in August 2020, with any potentially relevant studies categorised as awaiting classification. SELECTION CRITERIA: Randomised trials, non-randomised trials, controlled before-after studies, interrupted time series, and repeated measures studies that compared different payment methods for healthcare providers working in outpatient care settings. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We conducted a structured synthesis. We first categorised the payment methods comparisons and outcomes, and then described the effects of different types of payment methods on different outcome categories. Where feasible, we used meta-analysis to synthesise the effects of payment interventions under the same category. Where it was not possible to perform meta-analysis, we have reported means/medians and full ranges of the available point estimates. We have reported the risk ratio (RR) for dichotomous outcomes and the relative difference (as per cent change or mean difference (MD)) for continuous outcomes. MAIN RESULTS: We included 27 studies in the review: 12 randomised trials, 13 controlled before-and-after studies, one interrupted time series, and one repeated measure study. Most healthcare providers were primary care physicians. Most of the payment methods were implemented by health insurance schemes in high-income countries, with only one study from a low- or middle-income country. The included studies were categorised into four groups based on comparisons of different payment methods. (1) Pay for performance (P4P) plus existing payment methods compared with existing payment methods for healthcare providers working in outpatient healthcare settings P4P incentives probably improve child immunisation status (RR 1.27, 95% confidence interval (CI) 1.19 to 1.36; 3760 patients; moderate-certainty evidence) and may slightly increase the number of patients who are asked more detailed questions on their disease by their pharmacist (MD 1.24, 95% CI 0.93 to 1.54; 454 patients; low-certainty evidence). P4P may slightly improve primary care physicians' prescribing of guideline-recommended antihypertensive medicines compared with an existing payment method (RR 1.07, 95% CI 1.02 to 1.12; 362 patients; low-certainty evidence). We are uncertain about the effects of extra P4P incentives on mean blood pressure reduction for patients and costs for providing services compared with an existing payment method (very low-certainty evidence). Outcomes related to workload or other health professional outcomes were not reported in the included studies. One randomised trial found that compared to the control group, the performance of incentivised professionals was not sustained after the P4P intervention had ended. (2) Fee for service (FFS) compared with existing payment methods for healthcare providers working in outpatient healthcare settings We are uncertain about the effect of FFS on the quantity of health services delivered (outpatient visits and hospitalisations), patient health outcomes, and total drugs cost compared to an existing payment method due to very low-certainty evidence. The quality of service provision and health professional outcomes were not reported in the included studies. One randomised trial reported that physicians paid via FFS may see more well patients than salaried physicians (low-certainty evidence), possibly implying that more unnecessary services were delivered through FFS. (3) FFS mixed with existing payment methods compared with existing payment methods for healthcare providers working in outpatient healthcare settings FFS mixed payment method may increase the quantity of health services provided compared with an existing payment method (RR 1.37, 95% CI 1.07 to 1.76; low-certainty evidence). We are uncertain about the effect of FFS mixed payment on quality of services provided, patient health outcomes, and health professional outcomes compared with an existing payment method due to very low-certainty evidence. Cost outcomes and adverse effects were not reported in the included studies. (4) Enhanced FFS compared with FFS for healthcare providers working in outpatient healthcare settings Enhanced FFS (higher FFS payment) probably increases child immunisation rates (RR 1.25, 95% CI 1.06 to 1.48; moderate-certainty evidence). We are uncertain whether higher FFS payment results in more primary care visits and about the effect of enhanced FFS on the net expenditure per year on covered children with regular FFS (very low-certainty evidence). Quality of service provision, patient outcomes, health professional outcomes, and adverse effects were not reported in the included studies. AUTHORS' CONCLUSIONS: For healthcare providers working in outpatient healthcare settings, P4P or an increase in FFS payment level probably increases the quantity of health service provision (moderate-certainty evidence), and P4P may slightly improve the quality of service provision for targeted conditions (low-certainty evidence). The effects of changes in payment methods on health outcomes is uncertain due to very low-certainty evidence. Information to explore the influence of specific payment method design features, such as the size of incentives and type of performance measures, was insufficient. Furthermore, due to limited and very low-certainty evidence, it is uncertain if changing payment models without including additional funding for professionals would have similar effects. There is a need for further well-conducted research on payment methods for healthcare providers working in outpatient healthcare settings in low- and middle-income countries; more studies comparing the impacts of different designs of the same payment method; and studies that consider the unintended consequences of payment interventions.

Comprehensive evaluation on anti-inflammatory and anti-angiogenic activities in vitro of fourteen flavonoids from Daphne Genkwa based on the combination of efficacy coefficient method and principal component analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Genkwa flos, as a traditional herb, is the dried flower buds of Daphne genkwa Sieb.et Zucc. It is used in traditional medicine for the treatment of cough, sore throats, edema. AIM OF THE STUDY: The study aimed to explore a new mathematical method for multivariate evaluation, investigate the anti-inflammatory and anti-angiogenic activities of flavonoids in Daphne Genkwa under ex vivo conditions. MATERIALS AND METHODS: The flavonoids monomers in Daphne Genkwa were separated by preparative liquid chromatography and identified by HPLC-ESI-ITMS. An in vitro inflammatory model of macrophage RAW264.7 induced by LPS and an angiogenesis model of human umbilical vein endothelial cells induced by TNF-α were established. Flavonoids were extracted and prepared for intervention to detect the amount of secretion after drug intervention to reflect the anti-inflammatory and anti-angiogenic activities of each component. In addition, a new mathematical method, which combined principal component analysis and efficacy coefficient method, was adopted in pharmacodynamic evaluation. RESULTS: Fourteen flavonoids monomers were separated by preparative liquid chromatography and identified by HPLC-ESI-ITMS including H1 (hydroxygenkwanin-5-O-ß-D-glucoside), H2 (apigenin-7-O-ß-D-glucoside), H3 (kaempferol-3-O-ß-D-glucoside), H4 (hydroxygenkwanin-5-O-ß-D-primeveroside), H5 (apigenin-5-O-ß-D-primeveroside), H6 (apigenin-7-O-ß-D-glucuronide), H7 (luteolin-5-O-ß-D-glucopyranoside), H8 (genkwain-5-O-ß-D- glucoside), H9 (luteolin), H10 (Daphnodorin G), H11 (tiliroside), H12 (apigenin), H13 (3'- hydroxygenkwain) and H14 (genkwanin). We found that most of flavonoids down-regulated VCAM and MMP-3, while H1, H8, H9, H14 reduced VEGF and ICAM was only decreased by H14. CONCLUSION: Genkwanin may be the most active anti-rheumatoid arthritis flavonoids in Daphne genkwa. Meanwhile, the new mathematical method used in the study provided a new direction for solving the problem of multi-index pharmacodynamic evaluation.

Clinical effectiveness of Er,Cr:YSGG lasers in non-surgical treatment of chronic periodontitis: a meta-analysis of randomized controlled trials.

The meta-analysis aimed to systematically evaluate all the available pieces of evidence concerning the clinical effectiveness of Er,Cr:YSGG lasers (erbium, chromium, yttrium scandium gallium garnet laser) in the non-surgical treatment of patients with chronic periodontitis, and provide guidance for clinicians about the application of Er,Cr:YSGG lasers during the process of non-surgical periodontal treatments. The meta-analysis was conducted with data extracted from 16 randomized controlled clinical trials (RCTs) that compare Er,Cr:YSGG lasers adjunct/substitute to scaling and root planing (SRP) with SRP alone for the treatment of chronic periodontitis published in English or Chinese from January 2000 to January 2020. The weighted mean differences (WMDs) and 95% confidence intervals (CIs) were counted for probing depth (PD) reduction, clinical attachment level (CAL) gain, and visual analogue scale (VAS) score. Heterogeneity of each study was evaluated with the Q test. The publication bias was measured using Begg's adjusted rank correlation test. Sixteen RCTs with 606 patients were included in the meta-analysis. There were statistically significant differences between Er,Cr:YSGG lasers adjunct/substitute to SRP and SRP alone in the PD reduction at 1-month follow-up (WMD = ­ 0.35, 95% CI [- 0.63, ­ 0.07], P = 0.013), 3-month follow-up (WMD = - 0.342, 95% CI [- 0.552, - 0.132], P = 0.001), CAL gain at 3-month follow-up (WMD = - 0.17, 95% CI [- 0.31, 0.03], P = 0.017), and VAS score (WMD = - 2.395, 95% CI [- 3.327, - 1.464], P = 0.000) immediately after treatment. There were no significant differences of PD reduction and CAL change at 6-month follow-up. The present meta-analysis indicated that Er,Cr:YSGG lasers provided additional effectiveness in PD reduction and CAL gain at short-term follow-ups and there was less pain compared with SRP alone.

Clinical attachment level gain of lasers in scaling and root planing of chronic periodontitis: a network meta-analysis of randomized controlled clinical trials.

The objective of this study was to evaluate the clinical attachment level (CAL) gain of Er:YAG, Er,Cr; YSGG, Nd:YAG; and diode laser (DL) as monotherapy or adjunctive to scaling and root planing (SRP) of chronic periodontitis by network meta-analysis (NMA). Randomized controlled clinical trials (RCTs) about lasers applied in SRP of chronic periodontitis were searched from PubMed, Cochrane Library, Web of Science, Ovid, Science Direct, Wan Fang, and China National Knowledge Infrastructure (CNKI) databases up to September 2018 and from references of selected full-texts and related reviews. Standard mean differences and 95% confidence intervals were counted for CAL gain. The random effects NMA were performed in STATA software. There were 25 RCTs about CAL gain at 3 and/or 6 months after lasers were applied in SRP. No inconsistency was detected. Er:YAG as monotherapy gained significantly more CAL at 3 months than did SRP; no significant differences were detected among other comparisons. In terms of CAL gain at 3 months, the ranking result from best to worst was as follows: Er:YAG as monotherapy, DL adjunctive to SRP, Er:YAG adjunctive to SRP, Er,Cr;YSGG as monotherapy, Nd:YAG adjunctive to SRP, and SRP. In terms of CAL gain at 6 months, the ranking result from best to worst was as follows: DL adjunctive to SRP, Nd:YAG adjunctive to SRP, SRP, Er:YAG adjunctive to SRP, and Er:YAG as monotherapy. Laser-assisted periodontal treatment could be superior to SRP alone and could serve as a good adjunctive treatment tool.

The Clinical Effectiveness of Calcium Hydroxide in Root Canal Disinfection of Primary Teeth: A Meta-Analysis.

BACKGROUND The aim of this research was to systematically analyze the effectiveness of calcium hydroxide compared to formocresol (FC) and camphor phenol (CP) in root canal disinfection of primary teeth. MATERIAL AND METHODS The meta-analysis was based on the participants, interventions, control, outcome (PICO) study design principle and 16 randomized-controlled clinical trials published from January 2000 to August 2018. The data heterogeneity of each study was assessed by the Q-test. The odds ratio and 95% confidence interval (CI) were calculated based on the heterogeneity results by Revman software. RESULTS Sixteen randomized-controlled clinical trials of 3047 primary teeth were included in this meta-analysis. There were significant differences of clinical effectiveness between calcium hydroxide and FC in root canal disinfection of primary teeth (OR=3.37; 95% CI range: 2.54-4.48, P<0.01) and endodontic inter-appointment emergencies (EIAE) after disinfection for 7 days (OR=0.26; 95% CI range: 0.16-0.42, P<0.01). However, there was no statistical difference of EIAE, after disinfection of primary teeth for 48 hours, between calcium hydroxide and FC (OR=0.62; 95% CI range: 0.34-1.11, P=0.11). There were significant differences of clinical effectiveness between the calcium hydroxide and CP in root canal disinfection of primary teeth (OR=5.50; 95% CI range: 3.36-8.98, P<0.01). CONCLUSIONS This meta-analysis indicated that the effectiveness of calcium hydroxide as root canal disinfectant in primary teeth was more effective than that of FC and CP.

Molecular cloning, characterization and expression analysis of spexin in spotted scat (Scatophagus argus).

Spexin (Spx), a novel neuropeptide, composed of 14 amino acid residues, is evolutionally conserved from fish to mammals. It has been suggested that Spx has pleiotropic functions in mammals. However, reports about Spx are very limited. To clarify the roles of Spx in the regulation of reproduction and food-intake in the spotted scat, the spx (ssspx) gene was cloned and analyzed. Analysis of the tissue distribution by RT-PCR showed that ssspx expression was widespread. During ovary development, expression of ssspx was found to be highest in phase II, moderate in phase III, and at its lowest level in phase IV. Ssspx expression was significantly down-regulated in the hypothalamus after treatment with E2 both in vitro and in vivo. A significant increase of ssspx was observed after 2 and 7 days of food deprivation. However, the ssspx transcript levels in the 7 day fasting group decreased significantly after refeeding 3 h after the scheduled feeding time. This suggests that ssSpx may be involved in the regulation of reproduction and food-intake in the spotted scat.

Correlation between microRNA-143 in peripheral blood mononuclear cells and disease severity in patients with psoriasis vulgaris.

This study aims to explore the correlation between microRNA-143 (miR-143) expression in peripheral blood mononuclear cells (PBMCs) and disease severity in patients with psoriasis vulgaris. From March 2014 to November 2015, 194 patients with psoriasis vulgaris (102 patients in progressive stage and 92 patients in stable stage) were selected as the case group and 175 healthy people as a control group were enrolled in this study. ELISA was used to detect the levels of IL-17 and VEGF in serum. The qRT-PCR assay was performed to detect the relative expression of miR-143 in PBMCs. Disease severity in psoriasis vulgaris patients was graded with Psoriasis Lesions Area and Severity Index (PASI). The value of miR-143 expression in PBMCs for the diagnosis of psoriasis vulgaris was evaluated using receiver operating characteristic (ROC) curve. The correlation between miR-143 expression in PBMCs and PASI scores was measured using Spearman rank correlation analysis. Compared with the control group, serum levels of IL-17 and VEGF were higher and miR-143 expression in PBMCs was lower in the case group. Furthermore, miR-143 expression in PBMCs was lower in patients in progressive stage than that in patients with stable stage. The relative expression of miR-143 in PBMCs was negatively correlated with PASI scores of patients with psoriasis vulgaris. ROC curve showed that miR-143 was a reliable and accurate biomarker of psoriasis vulgaris. Our findings suggest that miR-143 expression in PBMCs is negatively correlated the disease severity in psoriasis vulgaris.

Payment methods for outpatient care facilities.

BACKGROUND: Outpatient care facilities provide a variety of basic healthcare services to individuals who do not require hospitalisation or institutionalisation, and are usually the patient's first contact. The provision of outpatient care contributes to immediate and large gains in health status, and a large portion of total health expenditure goes to outpatient healthcare services. Payment method is one of the most important incentive methods applied by purchasers to guide the performance of outpatient care providers. OBJECTIVES: To assess the impact of different payment methods on the performance of outpatient care facilities and to analyse the differences in impact of payment methods in different settings. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), 2016, Issue 3, part of the Cochrane Library (searched 8 March 2016); MEDLINE, OvidSP (searched 8 March 2016); Embase, OvidSP (searched 24 April 2014); PubMed (NCBI) (searched 8 March 2016); Dissertations and Theses Database, ProQuest (searched 8 March 2016); Conference Proceedings Citation Index (ISI Web of Science) (searched 8 March 2016); IDEAS (searched 8 March 2016); EconLit, ProQuest (searched 8 March 2016); POPLINE, K4Health (searched 8 March 2016); China National Knowledge Infrastructure (searched 8 March 2016); Chinese Medicine Premier (searched 8 March 2016); OpenGrey (searched 8 March 2016); ClinicalTrials.gov, US National Institutes of Health (NIH) (searched 8 March 2016); World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (searched 8 March 2016); and the website of the World Bank (searched 8 March 2016).In addition, we searched the reference lists of included studies and carried out a citation search for the included studies via ISI Web of Science to find other potentially relevant studies. We also contacted authors of the main included studies regarding any further published or unpublished work. SELECTION CRITERIA: Randomised trials, non-randomised trials, controlled before-after studies, interrupted time series, and repeated measures studies that compared different payment methods for outpatient health facilities. We defined outpatient care facilities in this review as facilities that provide health services to individuals who do not require hospitalisation or institutionalisation. We only included methods used to transfer funds from the purchaser of healthcare services to health facilities (including groups of individual professionals). These include global budgets, line-item budgets, capitation, fee-for-service (fixed and unconstrained), pay for performance, and mixed payment. The primary outcomes were service provision outcomes, patient outcomes, healthcare provider outcomes, costs for providers, and any adverse effects. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data and assessed the risk of bias. We conducted a structured synthesis. We first categorised the comparisons and outcomes and then described the effects of different types of payment methods on different categories of outcomes. We used a fixed-effect model for meta-analysis within a study if a study included more than one indicator in the same category of outcomes. We used a random-effects model for meta-analysis across studies. If the data for meta-analysis were not available in some studies, we calculated the median and interquartile range. We reported the risk ratio (RR) for dichotomous outcomes and the relative change for continuous outcomes. MAIN RESULTS: We included 21 studies from Afghanistan, Burundi, China, Democratic Republic of Congo, Rwanda, Tanzania, the United Kingdom, and the United States of health facilities providing primary health care and mental health care. There were three kinds of payment comparisons. 1) Pay for performance (P4P) combined with some existing payment method (capitation or different kinds of input-based payment) compared to the existing payment methodWe included 18 studies in this comparison, however we did not include five studies in the effects analysis due to high risk of bias. From the 13 studies, we found that the extra P4P incentives probably slightly improved the health professionals' use of some tests and treatments (adjusted RR median = 1.095, range 1.01 to 1.17; moderate-certainty evidence), and probably led to little or no difference in adherence to quality assurance criteria (adjusted percentage change median = -1.345%, range -8.49% to 5.8%; moderate-certainty evidence). We also found that P4P incentives may have led to little or no difference in patients' utilisation of health services (adjusted RR median = 1.01, range 0.96 to 1.15; low-certainty evidence) and may have led to little or no difference in the control of blood pressure or cholesterol (adjusted RR = 1.01, range 0.98 to 1.04; low-certainty evidence). 2) Capitation combined with P4P compared to fee-for-service (FFS)One study found that compared with FFS, a capitated budget combined with payment based on providers' performance on antibiotic prescriptions and patient satisfaction probably slightly reduced antibiotic prescriptions in primary health facilities (adjusted RR 0.84, 95% confidence interval 0.74 to 0.96; moderate-certainty evidence). 3) Capitation compared to FFSTwo studies compared capitation to FFS in mental health centres in the United States. Based on these studies, the effects of capitation compared to FFS on the utilisation and costs of services were uncertain (very low-certainty evidence). AUTHORS' CONCLUSIONS: Our review found that if policymakers intend to apply P4P incentives to pay health facilities providing outpatient services, this intervention will probably lead to a slight improvement in health professionals' use of tests or treatments, particularly for chronic diseases. However, it may lead to little or no improvement in patients' utilisation of health services or health outcomes. When considering using P4P to improve the performance of health facilities, policymakers should carefully consider each component of their P4P design, including the choice of performance measures, the performance target, payment frequency, if there will be additional funding, whether the payment level is sufficient to change the behaviours of health providers, and whether the payment to facilities will be allocated to individual professionals. Unfortunately, the studies included in this review did not help to inform those considerations.Well-designed comparisons of different payment methods for outpatient health facilities in low- and middle-income countries and studies directly comparing different designs (e.g. different payment levels) of the same payment method (e.g. P4P or FFS) are needed.

Serum leptin level measured 48 h after delivery is associated with development of postpartum depressive symptoms: a 3-month follow-up study.

The aim of this study was to assess the possible relationship between leptin status and postpartum depressive symptoms using serum levels of leptin collected 24-48 h after delivery in a cohort Chinese sample. Women delivering a full-term, singleton, and live-born infant in the period from August 2013 to March 2014 were enrolled immediately postpartum. A blood sample was obtained 24-48 h after childbirth to test serum levels of leptin. Participation consisted of a visit in an obstetric unit at 3 months after delivery. The Edinburgh Postnatal Depression Scale (EPDS), completed at 3 months postpartum, was used to classify each woman's depression symptom severity. Demographic, obstetric, behavioral risk, mental health, and psychosocial factors were considered. Multiple logistic regression analyses were used to identify risk factors most predictive of postpartum depressive symptoms. During the study period, 407 individuals were included and completed follow-up. At 3 months, according to EPDS score, 53 women (13.0 %) were considered as postpartum depressive symptoms. Serum leptin levels in women with PPD were significantly greater than those in women without depressive symptoms (36.5 [IQR, 25.5-50.4] vs. 14.5 [IQR, 9.4-22.4] ng/ml, P < 0.0001). Based on the ROC curve, the optimal cutoff value of serum leptin levels as an indicator for predicting of depressive symptoms was projected to be 24.3 ng/mL, which yielded a sensitivity of 88.7 % and a specificity of 73.4 %, with the area under the curve at 0.867 (95 % CI, 0.817-0.916). In multivariate analysis, there was an increased risk of depressive symptoms associated with leptin levels ≥24.3 ng/ml (OR 8.234; 95 % CI, 3.572-15.876; P < 0.0001) after adjusting for possible confounders. Elevated serum leptin levels at delivery could eventually serve as a biological marker for the prediction of depressive symptoms. These associations were independent of other possible variables.

Strategies for expanding health insurance coverage in vulnerable populations.

BACKGROUND: Health insurance has the potential to improve access to health care and protect people from the financial risks of diseases. However, health insurance coverage is often low, particularly for people most in need of protection, including children and other vulnerable populations. OBJECTIVES: To assess the effectiveness of strategies for expanding health insurance coverage in vulnerable populations. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL), part of The Cochrane Library. www.thecochranelibrary.com (searched 2 November 2012), PubMed (searched 1 November 2012), EMBASE (searched 6 July 2012), Global Health (searched 6 July 2012), IBSS (searched 6 July 2012), WHO Library Database (WHOLIS) (searched 1 November 2012), IDEAS (searched 1 November 2012), ISI-Proceedings (searched 1 November 2012),OpenGrey (changed from OpenSIGLE) (searched 1 November 2012), African Index Medicus (searched 1 November 2012), BLDS (searched 1 November 2012), Econlit (searched 1 November 2012), ELDIS (searched 1 November 2012), ERIC (searched 1 November 2012), HERDIN NeON Database (searched 1 November 2012), IndMED (searched 1 November 2012), JSTOR (searched 1 November 2012), LILACS(searched 1 November 2012), NTIS (searched 1 November 2012), PAIS (searched 6 July 2012), Popline (searched 1 November 2012), ProQuest Dissertation &Theses Database (searched 1 November 2012), PsycINFO (searched 6 July 2012), SSRN (searched 1 November 2012), Thai Index Medicus (searched 1 November 2012), World Bank (searched 2 November 2012), WanFang (searched 3 November 2012), China National Knowledge Infrastructure (CHKD-CNKI) (searched 2 November 2012).In addition, we searched the reference lists of included studies and carried out a citation search for the included studies via Web of Science to find other potentially relevant studies. SELECTION CRITERIA: Randomised controlled trials (RCTs), non-randomised controlled trials (NRCTs), controlled before-after (CBA) studies and Interrupted time series (ITS) studies that evaluated the effects of strategies on increasing health insurance coverage for vulnerable populations. We defined strategies as measures to improve the enrolment of vulnerable populations into health insurance schemes. Two categories and six specified strategies were identified as the interventions. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data and assessed the risk of bias. We undertook a structured synthesis. MAIN RESULTS: We included two studies, both from the United States. People offered health insurance information and application support by community-based case managers were probably more likely to enrol their children into health insurance programmes (risk ratio (RR) 1.68, 95% confidence interval (CI) 1.44 to 1.96, moderate quality evidence) and were probably more likely to continue insuring their children (RR 2.59, 95% CI 1.95 to 3.44, moderate quality evidence). Of all the children that were insured, those in the intervention group may have been insured quicker (47.3 fewer days, 95% CI 20.6 to 74.0 fewer days, low quality evidence) and parents may have been more satisfied on average (satisfaction score average difference 1.07, 95% CI 0.72 to 1.42, low quality evidence).In the second study applications were handed out in emergency departments at hospitals, compared to not handing out applications, and may have had an effect on enrolment (RR 1.5, 95% CI 1.03 to 2.18, low quality evidence). AUTHORS' CONCLUSIONS: Community-based case managers who provide health insurance information, application support, and negotiate with the insurer probably increase enrolment of children in health insurance schemes. However, the transferability of this intervention to other populations or other settings is uncertain. Handing out insurance application materials in hospital emergency departments may help increase the enrolment of children in health insurance schemes. Further studies evaluating the effectiveness of different strategies for expanding health insurance coverage in vulnerable population are needed in different settings, with careful attention given to study design.

[Clinical analysis of uterine rupture during pregnancy].

OBJECTIVE: To explore the clinical characteristics of pregnant uterine rupture, enhance its early diagnosis rate and improve its prognosis. METHODS: For this retrospective study, a total of 55 143 delivery cases at Tongzhou District Maternal & Child Health Hospital from January 1, 2003 to May 31, 2012 was analyzed. There were 2490 cases of scarred uterus and 68 cases had uterine rupture. And 62 of them belonged to scarred uterus rupture. And there were 52 653 cases of non-scarred uterus childbirth and 6 of them had rupture. RESULTS: Significant differences existed in the rupture of scarred versus non-scarred uterus and maternal versus primipara women. Uterus rupture usually occurred at the incomplete rupture position of original surgical scar at 39 weeks or more. The scar thickness of lower uterine segment was ≤ 3 mm on ultrasound. Three cases with laparoscopic myoma removal within 1 year had complete rupture at 36-38 weeks. Postpartum hemorrhage incidence was 42.65%. There were two cases of hysterectomy and 11 cases of neonatal asphyxia. CONCLUSION: For second pregnancy of cesarean section, pregnancy should be terminated before 39 weeks if scar thickness of lower uterine segment is ≤ 3 mm. Late rupture is to be monitored closely for those with laparoscopic myoma removal within 1 year. Meanwhile, we should strengthen the management of migrant and unemployed women.