Pioglitazone alleviates lacrimal gland impairments induced by high-fat diet by suppressing M1 polarization.

A high-fat diet (HFD) contributes to the pathogenesis of various inflammatory and metabolic diseases. Previous research confirms that under HFD conditions, the extraorbital lacrimal glands (ELGs) can be impaired, with significant infiltration of pro-inflammatory macrophages (Mps). However, the relationship between HFD and Mps polarization in the ELGs remains unexplored. We first identified and validated the differential expression of PPAR-γ in murine ELGs fed ND and HFD through RNA sequencing. Tear secretion was measured using the Schirmer test. Lipid droplet deposition within the ELGs was observed through Oil Red O staining and transmission electron microscopy. Mps phenotypes were determined through quantitative RT-PCR, immunofluorescence, and flow cytometric analysis. An in vitro high-fat culture system for Mps was established using palmitic acid (PA), with supernatants collected for co-culture with lacrimal gland acinar cells. Gene expression was determined through ELISA, immunofluorescence, immunohistochemistry, quantitative RT-PCR, and Western blot analysis. Pioglitazone reduced M1-predominant infiltration induced by HFD by increasing PPAR-γ levels in ELGs, thereby alleviating lipid deposition and enhancing tear secretion. In vitro tests indicated that PPAR-γ agonist shifted Mps from M1-predominant to M2-predominant phenotype in PA-induced Mps, reducing lipid synthesis in LGACs and promoting lipid catabolism, thus alleviating lipid metabolic disorders within ELGs. Conversely, the PPAR-γ antagonist induced opposite effects. In summary, the lacrimal gland is highly sensitive to high-fat and lipid metabolic disorders. Downregulation of PPAR-γ expression in ELGs induces Mps polarization toward predominantly M1 phenotype, leading to lipid metabolic disorder and inflammatory responses via the NF-κb/ERK/JNK/P38 pathway.

[Guidelines for construction of traditional Chinese medicine pharmacovigilance system in medical institutions].

The group standard Guidelines for construction of traditional Chinese medicine(TCM) pharmacovigilance system in medical institutions, managed by Chinese Association of Chinese Medicine and led by the Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences and Dongfang Hospital of Beijing University of Chinese Medicine, was announced on National Group Standard Information Platform on January 16, 2024, with the standard number T/CACM 1563. 2-2024. According to EU pharmacovigilance regulations and the second-level guidance principles of International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH), the unique characteristics of TCM were fully considered, and the relevant systems and procedures for constructing TCM pharmacovigilance systems in medical institutions were clearly defined. This included establishing TCM pharmacovigilance information platforms, arranging staff, formulating various regulations, and monitoring adverse reactions of TCM(including TCM decoction pieces, granules, Chinese patent medicines, in-hospital preparations, and pre-marketed Chinese patent medicines). It aimed to develop a TCM pharmacovigilance system in medical institutions that was tailored to the characteristics of TCM. The system could be appropriately adjusted according to the scope of practice and actual circumstances of medical institutions at different levels. This will enhance the implementation of TCM pharmacovigilance work and safeguard medication safety. The group standard underwent multiple rounds of consultations with internal and external experts and has ultimately evolved into a guiding document applicable to medical institutions and related entities engaged in pharmacovigilance activities.

[Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines].

Oral Chinese patent medicine is the essence of effective prescriptions created and summarized by Chinese medical scientists through thousands of years of medical practice. It is portable and convenient, with an obvious curative effect and other characteristics. However, at present, oral Chinese patent medicine is rich in dosage forms, various in types, complex in mechanism of action, and broad in clinical positioning. In clinical application, there are often cases of drug use without reference to instructions,repeated drug use, and prolonged drug use, which highlights safety problems such as adverse reactions and hepatorenal toxicity. Oral Chinese patent medicine pharmacovigilance is facing challenges. World Health Organization(WHO) has issued the WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems, and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH) has issued the ICH E2 pharmacovigilance guidelines. The United States has issued the Pharmacovigilance management standards and pharmacoepidemiological assessment guidelines, and the European Union has issued the Guidelines on good pharmacovigilance practices. Japan, South Korea, and other countries in the Asia Pacific region have established their own pharmacovigilance systems, but currently, there are no pharmacovigilance guidelines related to oral Chinese patent medicine in China. Therefore, experts from many disciplines and fields in China were invited to jointly develop the Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines, which aims to develop pharmacovigilance guidelines for clinical application that are consistent with China's national conditions and highlight the characteristics of oral Chinese patent medicine, and provide guidance for clinically safe and rational drug application in medical institutions.

[Pharmacovigilance guidelines of Chinese patent medicines].

Drug administration law of the People's Republic of China(2019 revised edition), which came into effect on December 1, 2019, proposed that " the state shall establish a pharmacovigilance system". Pharmacovigilance work of Chinese patent medicines is more difficult, and it is necessary to carry out Pharmacovigilance activities that are in line with the characteristics of Chinese patent medicines. Pharmacovigilance guidelines of Chinese patent medicines(T/CACM 1563. 1-2024), based on the principles of Drug Administration Law of the People's Republic of China(2019 revised edition) and Pharmacovigilance quality management standards(No. 65 of 2021) of the National Medical Products Administration, draws on the EU Pharmacovigilance regulation and the secondary guidelines of International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH), and it is drafted in accordance with the provisions of Guidelines for standardization work part 1: structure and drafting rules of standardization documents(GB/T1. 1-2020) based on the characteristics of Chinese patent medicines. It serves as a general document for a series of pharmacovigilance guidelines of Chinese patent medicines, such as Guidelines for construction of traditional Chinese medicine pharmacovigilance system in medical institutions(T/CACM 1563. 2-2024), Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines(T/CACM 1563. 3-2024), Pharmacovigilance guidelines for clinical application of traditional Chinese medicine injections(T/CACM 1563. 4-2024), Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use(T/CACM 1563. 5-2024), and Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration(T/CACM 1563. 6-2024), including four major elements of pharmacovigilance monitoring and reporting of Chinese patent medicines, signal identification, risk evaluation, and risk control, as well as pharmacovigilance activities for Chinese patent medicines, ensuring the safety of public drug use.

[Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration].

The group standard Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration was released on January 16, 2024, on the national group standards information platform by the Institute of Basic Research in Clinical Medicine of China Academy of Chinese Medical Sciences and School and Hospital of Stomatology of Peking University, under the centralized management by the China Association of Chinese Medicine. The standard number is T/CACM 1563.6-2024. It aims to propose key elements and specify technical methods for safety monitoring and reporting, signal identification, risk assessment, and risk control based on the Drug administration law of the People's Republic of China(revised in 2019), which establishes normative pharmacovigilance guideline of Chinese patent medicine for mucosal administration that is in line with the characteristics of traditional Chinese Medicine(TCM) based on the pharmacovigilance content for clinical application of Chinese patent medicine for mucosal administration. The group standard has been discussed by internal and external experts through multiple rounds of consultation. It serves as a guiding document for stakeholders involved in pharmacovigilance activities, including pharmaceutical license holders, drug manufacturers, medical institutions, research institutes, and pharmaceutical trading enterprises.

Epidemiology and survival outcomes of patients with primary intraocular lymphoma: a population-based analysis.

BACKGROUND: Primary intraocular lymphoma (PIOL) is a rare malignancy with a poor prognosis, but its optimal therapy remains unclear. Herein, we aimed to analyze the epidemiology and survival outcomes of PIOL patients based on a population-based cancer registry in the United States. METHODS: Patients diagnosed with PIOL between 1992 and 2018 were identified from the Surveillance Epidemiology and End Results program. The patients were divided into two groups: those aged < 60 years and ≥ 60 years. We used the chi-squared test to analyze the differences between the two groups. Descriptive analyses were performed to analyze epidemiological characteristics and treatment. The likely prognostic factors were analyzed by Kaplan-Meier curves and Cox proportional hazards models. RESULTS: The overall incidence of PIOL was 0.23/1,000,000, which was steadily increasing from 1992 to 2018, with an annual percentage change of 2.35. In total, 326 patients (mean age, 66.1 years) with PIOL were included in this study, 72.1% were aged ≥ 60 years, 84.4% were White, and 60.4% were female. The most common pathological type was diffuse large B-cell lymphoma (DLBCL), but in patients aged < 60 years, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue was the most common. The disease-specific survival rates were 74.2% and 61.5% 5 and 10 years after diagnosis, respectively. Survival analysis found that surgery, radiation, and chemotherapy did not lead to better prognosis. CONCLUSIONS: PIOL is a rare disease with poor prognosis, and its incidence has been increasing for nearly 30 years. It usually affects people aged ≥ 60 years, and DLBCL is the most common pathological type of PIOL. Patients aged < 60 years and with non-DLBCL type have improved survival. Survival of PIOL has improved in recent years.

[Pharmacoeconomic evaluation of Qidong Yixin Oral Liquid in treatment of viral myocarditis (Qi-Yin deficiency syndrome) with TreeAge Pro].

To evaluate the pharmacoeconomic value of Qidong Yixin Oral Liquid in the treatment of viral myocarditis(Qi-Yin deficiency syndrome) by supplementing Qi, nourishing the heart, calming the mind, and relieving palpitation, the present study performed the Meta-analysis based on the published papers on Qidong Yixin Oral Liquid by AMSTAR and carried out pharmacoeconomic evaluation using TreeAge Pro by the cost-effectiveness analysis. The results showed that the quality of the included papers was good. After four weeks of treatment, Qidong Yixin Oral Liquid combined with the conventional treatment regimen was superior to the conventional treatment in improving creatine kinase isoenzyme, and the difference was statistically significant. Furthermore, the treatment cost was also higher than that of conventional treatment, with an incremental cost-effectiveness ratio of CNY 95.89, accounting for 0.30% of per capita disposable income. The results of sensitivity analysis showed that the research results were robust. Therefore, based on the assumption that the per capita disposable income in 2020 was the threshold of patients' willingness to pay, it is more economical for patients with viral myocarditis to use Qidong Yixin Oral Liquid combined with conventional secondary prevention regimen than conventio-nal secondary prevention regimen alone. The economic evaluation of Qidong Yixin Oral Liquid in the treatment of viral myocarditis will help physicians and patients choose optimal treatment options, improve rational clinical medication, and provide references for the efficient allocation and utilization of medical resources in China.

[Cognition of traditional Chinese medicine properties and thinking of clinical rational use of drug].

This paper discusses the rational use of traditional Chinese medicine based on chemical composition, body state and biological effect. The essence and connotations of traditional Chinese medicine are explained by modern scientific theory and technical means, and the mechanism of traditional Chinese medicine in the treatment of diseases is defined in modern medicine language, which is conducive to promoting rational and safe clinical use of drugs. Based on the chemical composition of traditional Chinese medicine,the selected genuine medicinal materials were collected and processed in a standardized way, and then used in the combination with other traditional Chinese medicines, with the aim to improve the efficacy of traditional Chinese medicine in clinical indications, increase the advantages, eliminate the disadvantages, and adapt to flexible and safe clinical drug demands. Based on the body state elements, clinical diagnosis and treatment shall be patient-centered, and doctors shall distinguish the differences of pathogenesis, symptoms and diseases, and consider the drug contraindications of special groups. According to the " dose-effect-toxicity" relationship, doctors shall select the appropriate dosage form, control the drug dosage, balance the benefits and risks of drugs, and carry out appropriate medical treatment. Based on the biological effect elements and the regulatory mechanism of traditional Chinese medicine on the target and pathway of disease, traditional Chinese medicine shall strengthen the precise positioning, provide accurate treatment; evaluate the safety of traditional Chinese medicine combination, explore the adverse reaction mechanism, strengthen the clinical safety monitoring of traditional Chinese medicine, and guide the clinical rational use of drugs, in the expectation of ensuring the safe use of traditional Chinese medicine and maximize the clinical efficacy of traditional Chinese medicine.

[Clinical comprehensive evaluation of Wenxin Granules in treatment of arrhythmia with deficiency of Qi and Yin].

This study evaluated the safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine of Wenxin Granules in the treatment of arrhythmia(ventricular premature beat and atrial premature beat) with deficiency of Qi and Yin. The multi-criteria decision analysis(MCDA) model was adopted, and the criterion layer and index layer were weighted by experts. CSC v2.0 was used for clinical comprehensive evaluation. This study embodies the clinical value of Wenxin Granules, promotes its safe, effective and rational use, and provides a basis for national medical decision-making. The multi-source evidence shows that the major adverse reaction of Wenxin Granules is gastrointestinal damage. According to the available studies, Wenxin Granules has controllable risk and thus is rated as grade B in terms of safety. The systematic evaluation of effectiveness shows that compared with antiarrhythmic western medicine, Wenxin Granules demonstrates improved clinical efficacy and electrocardiogram efficacy, which is supported by high-quality evidence, and thus the effectiveness of Wenxin Granules is evaluated as grade A. Economic research shows that Wenxin Granules is more economical than antiarrhythmic western medicine, which is supported by sufficient evidence and clear results, and thus the economy of this preparation is rated as grade B. The indications and contraindications of Wenxin Granules are clear and detailed to different types of arrhythmia, which, together with the precise positioning and prominent clinical innovation and industrial innovation, rates it as grade A in terms of innovation. The suitability of drug storage, prescription circulation, dosage form and course of treatment basically meet the clinical medication needs of doctors and patients, and thus the suitability of Wenxin Granules is evaluated as grade B. Because of the few restrictions and the sustainable resources of medicinal materials, the accessibility of Wenxin Granules is evaluated as grade A. The prescription compatibility focuses on the pathogenesis characteristics of deficiency of Qi and Yin, and there are more than 3 000 cases studied. Therefore, the characteristics of traditional Chinese medicine of Wenxin Granules are evaluated as grade B. Based on the evidence from all the above dimensions, Wenxin Granules has the clinical comprehensive value of class A and prominent characteristics of traditional Chinese medicine. It is suggested to include Wenxin Granules into the policy results related to basic clinical medication management according to the procedure.

[Report standards for clinical comprehensive evaluation of Chinese patent medicine].

The clinical comprehensive evaluation of drugs is an important basis for the return of clinical value, decision-making of medical and health authorities, and allocation of medical resources. In July 2021, the National Health Commission issued the Guidelines for the Management of Clinical Comprehensive Evaluation of Drugs(trial version 2021), which required the evaluation to be implemented from the six dimensions(safety, effectiveness, economy, innovation, suitability, and accessibility), and made detailed arrangements for the clinical comprehensive evaluation of drugs. As Chinese patent medicine differs from chemical medicines in terms of effective components and action modes, the clinical comprehensive evaluation of Chinese patent medicine should highlight the characteristics and advantages of traditional Chinese medicine(TCM) on the basis of general requirements of comprehensive clinical evaluation of drugs. At present, in the clinical comprehensive evaluation of Chinese patent medicine, unified report standards have not yet been generated, resulting in the uneven quality of existing reports. To standardize the clinical comprehensive evaluation report of Chinese patent medicine and improve its quality, the editorial team, based on the relevant policy documents of clinical comprehensive evaluation of drugs, formulated the clinical comprehensive evaluation report standards for Chinese patent medicine in combination with the previous practice and expert opinions. The report standards, containing seven sections with 15 items determined, focus on data source, evaluation content, evidence synthesis, quality control, and evaluation results supported with detailed interpretations to help researchers better understand and apply the report standards for clinical comprehensive evaluation of Chinese patent medicine, improve the report quality, and provide references for the decision-making by the national medical management authorities.

[Study of integrative evidence chain in clinical trial of Guizhi Fuling Capsules based on "Yibing Tongzhi" in clinical applications].

Guizhi Fuling Capsules is a new-type traditional Chinese medicine preparation made by modern process method. It was widely used to treat uterine fibroids, pelvic inflammation, dysmenorrhea, endometriosis, mammary gland hyperplasia and other gynecological diseases. Under the combination of disease and syndrome, the diagnosis and treatment model of "Yizheng Tongbing, Yibing Tongzhi" with Chinese patent medicine has been widely used in clinical practice. Meanwhile, the effectiveness and safety have been given more and more attention. Based on the effectiveness of Guizhi Fuling Capsules, this paper preliminarily summarized the dominant diseases in randomized controlled trials and systematic reviews of Guizhi Fuling Capsules. On the basis of the basic theory of traditional Chinese medicine and modern pharmacological mechanism, the clinical efficacy and mechanism of Guizhi Fuling Capsules were explored. Finally, according to the traditional Chinese medicine theory of "Yizheng Tongbing, Yibing Tongzhi", all the clinical evidences were integrated to form an integrated evidence chain, so as to provide guidance for the safe and rational use of Guizhi Fuling Capsules.

Altered Corneal Nerves in Chinese Thyroid-Associated Ophthalmopathy Patients Observed by In Vivo Confocal Microscopy.

BACKGROUND Thyroid-associated ophthalmopathy (TAO) is a common endocrine autoimmune disease. The present study explored corneal nerve changes in TAO patients. MATERIAL AND METHODS Thirty-eight Chinese TAO patients and 20 healthy individuals were included in the study. Central corneal subbasal nerve density and morphology were evaluated with in vivo laser scanning confocal microscopy and quantified using automated CCmetrics software. RESULTS The values of the central corneal subbasal nerve plexus parameters of both active and inactive TAO patients were significantly decreased compared with those of controls, including corneal nerve fiber density (CNFD) (P<0.001 for both), corneal nerve branch density (CNBD) (P<0.001 for both), corneal nerve fiber length (CNFL) (P<0.001 for both), corneal nerve fiber total branch density (CTBD) (P<0.001 for both), corneal nerve fiber area (CNFA) (P<0.001 for both), corneal nerve fiber width (CNFW) (P=0.046, P=0.027, respectively), and corneal nerve fiber fractal dimension (ACNFrD) (P<0.001 for both). In addition, CNFD and ACNFrD values were significantly lower in the active TAO patients compared with those in the inactive TAO patients (P=0.020, P=0.002, respectively). There were significant correlations between CNFD, CNBD, CNFL, CTBD, CNFA, and ACNFrD and the ocular surface parameters and activity assessment items. CONCLUSIONS Abnormal corneal subbasal nerves were observed in both active and inactive Chinese TAO patients, suggesting that nerve degeneration is associated with the disease. However, the exact underlying mechanisms remain to be elucidated.

[Analysis on 1 500 adverse reactions of Guizhi Fuling Capsules based on spontaneous response system].

To understand the characteristics of adverse reactions and find early warning signs after intake of Guizhi Fuling Capsules. The 1 500 adverse reaction(ADR) cases of Guizhi Fuling Capsules obtained by spontaneous reporting system(SRS) from 2008 to 2017 were analyzed by proportional reporting ratios method(PRR), Bayesian confidence propagation neural network method(BCPNN) and propensity score method. The number of ADR reports increased year by year, and reached the peak in the fourth quarter of 2014. A total of 1 500 ADR cases were monitored, including 10 severe ADR cases. There were a total of 934 cases aged between 18-44 years old, accounting for 62.27%. All patients were orally administered. Among them, 1 398 patients received a single dose according to the package insert, and 57.4% had ADR within 24 h. The top five clinical manifestations of ADR were gastric dysfunction, abdominal pain, nausea, vomiting and rash, which mainly damaged the digestive system. The ADR signals were analyzed. PRR suggested that "gastric dysfunction" and "abdominal pain" were the early warning signals of Guizhi Fuling Capsules. BCPNN suggested that "nausea" and "abdominal pain" were the early warning signals of Guizhi Fuling Capsules. After the propensity score weighting method was used to control the confounding factors, the warning signals remained unchanged. The results show that Guizhi Fuling Capsules has fewer adverse reactions and is relatively safe. This study provides a basis for studying ADR of Guizhi Fuling Capsules, and guidance for drug vigilance and risk management of Guizhi Fuling Capsules.

[Analysis of Qingkailing Injection in treatment of combined medication features of 2 147 cases of upper respiratory tract infection].

Acute upper respiratory infection is one of the common infectious diseases,especially in the elderly people. Qingkailing Injection has the effect of clearing away heat and detoxifying. It can be used for external wind heat,upper respiratory tract infection,viral cold,etc. Based on 2 147 cases of upper respiratory tract infection patients using Qingkailing Injection in the medical electronic data warehouse of the information system of 16 large class-A hospitals constructed by the Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,description analysis,Apriori calculation and recurrent network analysis were used to analyze the effect of Qingkailing Injection on upper respiratory tract infection. The clinical characteristics and the law of combined use of drugs can provide reference for the mining of clinical diagnosis and treatment characteristics and the construction of optimal and effective programs and paths. 2 147 patients with upper respiratory tract infection who used Qingkailing Injection were mostly middle-aged and elderly people over 45 years old,often combined with hypertension,ischemic cerebrovascular disease,coronary heart disease,diabetes,etc.; in treatment,it was more common to use Qingkailing Injection in combination with hormones,antipyretics and analgesics,antibiotics,nutritional support agents,antitussive,expectorant and antiasthmatic drugs,as well as traditional Chinese medicine Jiebiao agents and blood management agents. The combination of potassium chloride injection and cephalosporin injection is the most commonly used in combination with two kinds of Western medicine( 33. 2%); the combination of Shuanghuanglian and Ganmao Qingre Granules is the most commonly used in combination with two kinds of traditional Chinese medicine( 9. 13%); through the calculation of complex network group module,it is found that Qingkailing Injection is often associated with antibiotics,antipyretic and analgesic drugs,antitussive,expectorant and antiasthmatic drugs,antiviral drugs and anti infection drugs. Drugs,nutritional support agents,bronchodilators,immunomodulators and other chemical drugs are often used in combination with Chinese medicine,such as Jiebiao agents,expectorants,Qingre agents,resuscitation agents,Qufeng agents,tonics,Liqi agents,which may be related to both the treatment of upper respiratory tract infection and the basic diseases of middle-aged and elderly patients,with the theoretical characteristics of " combination of disease and syndrome,corresponding formula and syndrome". Based on the real world big data complex network group module mining results provide clues for the clinical optimization scheme and path construction,and provide signals and ideas for further causal research.

[Post-marketing surveillance on Guizhi Fuling Jiaonang based on literature review].

To systemically evaluate the post-marketing safety of Guizhi Fuling Jiaonang. Computer retrieval was conducted in Medline, EMbase, the Web of Science, Clinical Trials. Gov, the Cochrane Library, CNKI, VIP, WanFang Data and CBM to collect relevant information. The papers were then screened according to inclusion and exclusion criteria. A total of 234 papers were included in this study, including 164 randomized controlled trials, 7 quasi-randomized controlled trials, 8 non-randomized controls, 56 case series, and 1 cohort study. The patients were only treated with Guizhi Fuling Jiaonang in 56 studies, and Guizhi Fuling Jiaonang was combined with other drugs in 178 studies. The total ADRs/AEs incidence was 1.99% in single use of Guizhi Fuling Jiaonang, and 8.21% in combined use, but showing no severe adverse reactions. Gastrointestinal system damage was most common in mild ADRs. In this study, it was found that the overall safety of Guizhi Fuling Jiaonang was acceptable. The direct evidences of the drug's safety case reports were systematically analyzed in this study, but the mechanism study on the safety of the drug after marketing or the prospective long-term clinical observation study was not sufficient, so the further studies on the safety of drug use should be conducted in order to provide better guidance for clinical medication.

Anti-vascular endothelial growth factor for control of wound healing in glaucoma surgery.

BACKGROUND: Trabeculectomy is performed as a treatment for glaucoma to lower intraocular pressure (IOP). The surgical procedure involves creating a channel through the wall of the eye. However scarring during wound healing can block this channel which will lead to the operation failing. Anti-vascular endothelial growth factor (VEGF) agents have been proposed to slow down healing response and scar formation. OBJECTIVES: To assess the effectiveness of anti-VEGF therapies administered by subconjunctival injection for the outcome of trabeculectomy at 12 months follow-up and to examine the balance of benefit and harms when compared to any other anti-scarring agents or no additional anti-scarring agents. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 12 November 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of anti-VEGF therapies administered by subconjunctival injection compared to any other anti-scarring agents or no additional anti-scarring agents (no treatment or placebo) in trabeculectomy surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcome was successful trabeculectomy at 12 months after surgery which was defined as achieving a target IOP (usually no more than 21 mm Hg) without any additional intervention. Other outcomes included: qualified success (achieving target IOP with or without additional intervention), mean IOP and adverse events. MAIN RESULTS: We included five RCTs (175 participants, 177 eyes) that met the inclusion criteria in this review.One trial conducted in Iran (37 participants, 37 eyes) compared anti-VEGF (bevacizumab 0.2 mg) versus control (sham injection) in people with refractory glaucoma. We judged this study to be at low risk of bias.The primary outcome of this review was not reported; mean IOP at three months was 15.1 mm Hg (standard deviation 1.0) in both anti-VEGF and control groups.Four trials compared anti-VEGF to mitomycin C (MMC) (138 particpants, 140 eyes). These studies were conducted in India, Iran, Turkey and the USA. The anti-VEGF agent used in these four trials was bevacizumab 2.5 mg (two trials), bevacizumab 1.25 mg three times and ranibizumab 0.5 mg. Two trials were at high risk of bias in two domains and one trial was at high risk of bias in four domains.Only one of these trials reported the primary outcome of this review (42 participants, 42 eyes). Low quality evidence from this trial showed that people receiving bevacizumab 2.5 mg during primary trabeculectomy were less likely to achieve complete success at 12 months compared to people receiving MMC but the confidence interval (CI) was wide and compatible with increased chance of complete success for anti-VEGF (risk ratio (RR) 0.71, 95% CI 0.46 to 1.08), Assuming that approximately 81% of people receiving MMC achieve complete success, the anticipated success using anti-VEGF agents would be between 37.2% and 87.4%. The same trial suggested no evidence for any difference in qualified success between bevacizumab and MMC (RR 1.00, 95% CI 0.87 to 1.14, moderate quality evidence). Two trials of primary trabeculectomy provided data on mean IOP at 12 months; one trial of bevacizumab 2.5 mg and one trial of ranibizumab 0.5 mg. Mean IOP was 1.86 mm Hg higher (95% CI 0.15 to 3.57) in the anti-VEGF groups compared to the MMC groups (66 people, low quality evidence). Data were reported on wound leak, hypotony, shallow anterior chamber and endophthalmitis, but these events occurred rarely and currently there are not enough data available to detect any differences, if any, between the two treatments. AUTHORS' CONCLUSIONS: The evidence is currently of low quality which is insufficient to refute or support anti-VEGF subconjunctival injection for control of wound healing in glaucoma surgery. The effect on IOP control of anti-VEGF agents in glaucoma patients undergoing trabeculectomy is still uncertain, compared to MMC.Further RCTs of anti-VEGF subconjunctival injection in glaucoma surgery are required, particularly compared to sham treatment with at least 12 months follow-up.

CD40 ligand induces expression of vascular cell adhesion molecule 1 and E-selectin in orbital fibroblasts from patients with Graves' orbitopathy.

PURPOSE: The aim of this study was to detect the effect of the CD40 ligand (CD40L) on the expression of vascular cell adhesion molecule 1 (VCAM-1) and E-Selectin in orbital fibroblasts (OFs) from patients with Graves' orbitopathy (GO), as well as the signaling pathways involved in this effect. METHODS: OFs were isolated from orbital tissues obtained from patients with severe GO who were undergoing orbital decompression surgery. VCAM-1 and E-selectin RNA and protein expression levels were quantified in OFs stimulated with soluble CD40L (sCD40L). RNA and protein quantification was performed with real-time polymerase chain reaction (PCR) and western blot analysis. Cytoplasmic and nuclear fractions were isolated in order to detect the nuclear translocation of nuclear factor-κB (NF-κB). Signaling pathway inhibitors were applied to determine the pathways involved. RESULTS: Compared to unstimulated OFs, the mRNA and protein levels of VCAM-1 and E-selectin in OFs incubated with sCD40L were significantly increased. This was observed in dose- and time-course experiments, and the inductive effects of sCD40L were much weaker in OFs from healthy donors. At the same time, we observed that CD40L induced nuclear translocation of NF-κB, also in a dose- and time-dependent manner. The up-regulation of VCAM-1 and E-selectin, as well as the NF-κB nuclear translocation induced by CD40L, was significantly attenuated by inhibitors targeting mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinase (PI3K), and NF-κB. CONCLUSIONS: CD40L demonstrated the ability to up-regulate the expression of VCAM-1 and E-selectin at the pre-translational level in OFs from patients with GO. The MAPK and PI3K pathways and NF-κB may play important roles in CD40L-induced VCAM-1 and E-selectin expression.

Meta-analysis of association between the -2578C/A polymorphism of the vascular endothelial growth factor and retinopathy in type 2 diabetes in Asians and Caucasians.

BACKGROUND AND OBJECTIVES: Vascular endothelial growth factor (VEGF) has been shown to play an important role in the development and progress of diabetic retinopathy (DR). A number of case-control studies focused on the association between VEGF -2578C/A and risk for DR. But the results were not always consistent, so we performed a meta-analysis to evaluate the precise association between this variant and risk for DR. METHODS: All publications on the association between VEGF -2578C/A polymorphism and DR were searched in the following electronic databases: PubMed, Embase, the Cochrane Library and Chinese Biomedical Literature Database, with the last report up to January 2013. This meta-analysis was assessed by Review Manager 5.1. RESULTS: A total of 6 studies were involved in this meta-analysis, including 835 cases and 867 controls. Overall, we found a significant association between this polymorphism and DR (A vs. C: OR=1.49, 95% CI=1.26-1.77, p<0.00001; AA vs. CA+CC: OR=1.26, 95% CI=0.94-1.68, p=0.12; AA+CA vs. CC: OR=1.56, 95% CI=1.27-1.91, p<0.00001; AA vs. CC: OR=1.67, 95% CI=1.20-2.32, p=0.003; CA vs. CC: OR=1.51, 95% CI=1.21-1.87, p=0.0002), but we did not find any significant association in Caucasians in subgroup analysis. The results were not materially altered after the studies which did not fulfill the Hardy-Weinberg equilibrium were excluded. CONCLUSION: Our meta-analysis supports the association between the VEGF -2578C/A polymorphism and DR, but not in the Caucasian population.

The prevalence of visual impairment in older adults in mainland China: a systematic review and meta-analysis.

PURPOSE: This paper presents estimates of the prevalence of blindness and low vision among older adults over 50 years of age in mainland China. METHODS: All primary reports of population-based studies that reported the prevalence or incidence of visual impairment among older populations in mainland China were identified. Twenty-four population-based studies were included in this systematic review. Blindness is defined as visual acuity of less than 3/60, or a corresponding visual-field loss to less than 10 degrees in the better eye with the best possible correction; low vision is defined as visual acuity of less than 6/18, but equal to or better than 3/60 in the better eye with the best possible correction. The pooled prevalence estimates of blindness and low vision were calculated assuming a random-effects model. Relative odds with 95% confidence intervals (95% CIs) were calculated, stratified by methodological and socioeconomic variables. RESULTS: The overall pooled prevalence of blindness was 1.7% (95% CI 1.4-2.1). The results of the meta-regression showed the significance of a predictor variable: geographic region. The blindness rates per 100 older adults in various regions were 1.4 (0.9-2.0) in East China, and 1.4 (1.0-2.0) in Central China and 2.5 (1.9-3.2) in Western China. The overall pooled prevalence of low vision was 4.1% (3.4-5.1) and the independent pooled prevalence rates stratified by geographic region were 3.6% (2.6-5.1) in East China, 3.6% (2.4-5.2) in Central China and 5.2% (3.6-7.4) in Western China. CONCLUSIONS: Blindness or low vision affects approximately 5.8% Chinese adults older than 50 years. The prevalence of visual impairment, and especially blindness, vary greatly by the developmental status of geographic region.