Population impact of fine particulate matter on tuberculosis risk in China: a causal inference.

BACKGROUND: Previous studies have suggested the potential association between air pollution and tuberculosis incidence, but this association remains inconclusive and evidence to assess causality is particularly lacking. We aimed to draw causal inference between fine particulate matter less than 2.5 µm in diameter (PM2.5) and tuberculosis in China. METHODS: Granger causality (GC) inference was performed within vector autoregressive models at levels and/or first-differences using annual national aggregated data during 1982-2019, annual provincial aggregated data during 1982-2019 and monthly provincial aggregated data during 2004-2018. Convergent cross-mapping (CCM) approach was used to determine the backbone nonlinear causal association based on the monthly provincial aggregated data during 2004-2018. Moreover, distributed lag nonlinear model (DLNM) was applied to quantify the causal effects. RESULTS: GC tests identified PM2.5 driving tuberculosis dynamics at national and provincial levels in Granger sense. Empirical dynamic modeling provided the CCM causal intensity of PM2.5 effect on tuberculosis at provincial level and demonstrated that PM2.5 had a positive effect on tuberculosis incidence. Then, DLNM estimation demonstrated that the PM2.5 exposure driven tuberculosis risk was concentration- and time-dependent in a nonlinear manner. This result still held in the multi-pollutant model. CONCLUSIONS: Causal inference showed that PM2.5 exposure driving tuberculosis, which showing a concentration gradient change. Air pollutant control may have potential public health benefit of decreasing tuberculosis burden.

The Effect of Statins on Levels of Dehydroepiandrosterone (DHEA) in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND Currently, statins are used to treat polycystic ovary syndrome (PCOS). This systematic review and meta-analysis aimed to investigate the effect of statins on serum or plasma levels of dehydroepiandrosterone (DHEA) in women with PCOS. MATERIAL AND METHODS Databases that were searched included PubMed, Embase, and the Cochrane Library from their inception to August of 2018. Published randomized controlled trials (RCTs) were identified that evaluated the impact of statins on plasma DHEA levels in women with PCOS. The Cochrane risk of bias tool was used to assess the quality of the included RCTs. A random-effects model was used to analyze the pooled results. RESULTS Meta-analysis was performed on data from ten published studies that included 735 patients and showed that statin treatment could significantly reduce plasma DHEA levels when compared with controls (SMD, -0.43; 95% CI, -0.81-0.06; p=0.02; I²=82%). Statins were significantly more effective than placebo in reducing the levels of DHEAs. Subgroup analysis based on statin type showed that atorvastatin significantly reduced DHEA levels (SMD, -0.63; 95% CI, -1.20 - -0.05; p=0.03; I²=38%) but simvastatin did not significantly reduce DHEA levels (SMD: -0.14; 95% CI, -0.49-0.28; p=0.43; I²=77%). Subgroup analysis based on duration of treatment showed no significant difference between 12 weeks of statin treatment (SMD, -0.61; 95% CI, -1.23-0.02; p=0.06; I²=85%) and 24 weeks (SMD, -0.34; 95% CI -0.95-0.28; p=0.29; I²=83%). CONCLUSIONS Meta-analysis showed that statins significantly reduced the levels of DHEA when compared with placebo in patients with PCOS.

[Metabolomics of bovine serum albumin-induced allergic reactions based on UPLC-Q-TOF-MS].

The metabonomic techniques were used to study the changes in endogenous metabolites between urines of rats in normal physiological conditions and bovine serum albumin induced allergic reactions, identify potential biomarkers associated with allergic reactions, and then analyze the metabolic pathways and the metabolic mechanisms of allergic reactions. The bovine serum albumin-induced allergic reactions in rats were adopted as a model to detect histamine and tryptase in rat serum and observe the issue morphology of lungs and trachea in rats. UPLC-Q-TOF-MS was applied in metabonomic analysis on urines between control group and allergic reaction model group. Principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were applied to observe the differences in metabolic profiling between urines of the two groups and select differential metabolites. There were significant differences in metabolism spectrum between the model group and the control group. Totally 14 differential metabolites and 4 major metabolic pathways were screened out. The metabonomic research method for urines of rats with bovine serum albumin-induced allergic reactions based on UPLC-Q-TOF-MS was established in this study. It was speculated that the mechanism of bovine serum albumin-induced allergic reactions may involve biosynthesis of isoflavone and folic acid and metabolism of tryptophan, nicotinic acid and nicotinamide. It lays a foundation for further exploration of the application of metabolomics in drug allergy reaction studies.

Diagnostic value of Procalcitonin, C-reactive protein-to-lymphocyte ratio (CLR), C-reactive protein and neutrophil-to-lymphocyte ratio (NLR) for predicting patients with Bacteraemia in the intensive care unit.

BACKGROUND: To explore the diagnostic value of procalcitonin (PCT), C-reactive protein-to-lymphocyte ratio (CLR), C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) for predicting patients with bacteremia in the intensive care unit (ICU). METHODS: This case-control study included 359 patients with suspected bacteremia were divided into a bacteremia group (n = 152) and a control group (n = 207) from September 2018 to April 2023. Patient data were collected using a laboratory information system (LIS). ROC curves for PCT, CLR, CRP, and NLR in predicting patients with bacteremia. RESULTS: For PCT, CLR, CRP and NLR to predict patients with bacteremia in the ICU, the AUCs were 0.991(95%CI: 0.974-0.998), 0.960(95%CI: 0.935-0.978), 0.955(95%CI: 0.928-0.974), and 0.898(95%CI:0.862-0.927), respectively; the optimal thresholds were 0.248 ng/mL, 47.52 mg/109, 48.32 mg/L, and 6.51, respectively; the sensitivities were 95.4(95%CI: 90.7-98.1), 88.2(95%CI: 81.9-92.8), 87.5(95%CI: 81.2-92.3), and 86.8(95%CI:80.4-91.8), respectively; and the specificities were 95.7(95%CI: 91.9-98.0), 90.8(95%CI: 86.0-94.4), 90.3(95%CI: 85.5-94.0), and 85.0(95%CI:79.4-89.6), respectively. The sensitivities of PCT, CLR, CRP and NLR for predicting bacteremia due to E. coli infection are as high as over 90%, the specificity of PCT is 100, and the sensitivity of NLR is 100. The sensitivity of CRP for predicting bacteremia due to non-Enterobacer infection is 100. CONCLUSIONS: Compared with those in the control group, PCT, CLR, CRP and NLR were significantly greater in the bacteremia group. The PCT, CLR, CRP, and NLR can all predict the occurrence of bacteremia. The PCT had the highest sensitivity and specificity in predicting bacteremia in ICU patients.

Cost-effectiveness of cytomegalovirus vaccination for females in China: A decision-analytical Markov study.

BACKGROUND: The global burden of disease caused by congenital cytomegalovirus (CMV) infection is high. Previous modeling studies have suggested that CMV vaccination may be cost-effective in developed countries. Congenital CMV infection is more likely driven by maternal non-primary infection in China. We aimed to measure the effectiveness and cost-effectiveness of population-level CMV vaccination in Chinese females. METHODS: A decision tree Markov model was developed to simulate potential CMV vaccination strategies in a multi-cohort setting, with a population size of 1,000,000 each for the infant, adolescent (10-year-old) and young adult (20-year-old) cohorts. The hypothetical vaccines were assumed to have 50% efficacy, 20 years of protection, 70% coverage, at a price of US$120/dose for base-case analysis. Costs and disability-adjusted life years (DALYs) were discounted by 3% per year and the vaccination would be considered cost-effective if an incremental cost-effectiveness ratio (ICER) was lower than 2021 Chinese per capita GDP (US$12,500). FINDINGS: For the pre-infection (PRI) vaccine efficacy type, the adolescent strategy was the most cost-effective, with an ICER of US$12,213 (12,134 to 12,291) pre DALY averted, compared with the next best strategy (young adult strategy). For pre- and post-infection (P&PI) efficacy type, the young adult strategy was the most cost-effective as it was cost-saving. In one-way analysis varying the PRI vaccine price, the infant strategy, adolescent strategy and the young adult strategy would be a dominant strategy over others if the vaccine cost ≤US$60, US$61-121 and US$122-251 per dose respectively. In contrast, the young adult strategy continued to be the preferred strategy until the P&PI vaccine price exceeded US$226/dose. Our main results were robust under a wide variety of sensitivity analyses and scenario analyses. INTERPRETATION: CMV vaccination for females would be cost-effective and even cost-saving in China. Our findings had public health implications for control of CMV diseases.

HDAC10 Inhibits Cervical Cancer Progression through Downregulating the HDAC10-microRNA-223-EPB41L3 Axis.

BACKGROUND: Although the tumorigenesis of cervical cancer (CC) has been widely investigated and recognized, the study of the systematic impact of histone deacetylase 10 (HDAC10), microRNA, and downstream molecular mechanisms in CC is still limited. Herein, cervical cancer, precancer lesions, and normal cervical tissues were collected to test the expression level of HDAC10, miR-223, and EPB41L3. The mechanism of HDAC10, miR-223, and EPB41L3 was interpreted in cervical cancer cells after HDAC10, miR-223, or EPB41L3 expression was altered. RESULTS: HDAC10 was poorly expressed in cervical cancer and precancer lesions, while miR-223 was highly expressed in cervical cancer. HDAC10 bound to miR-223, and miR-223 targeted EPB41L3. HDAC10 depressed the invasion property and tumorigenesis of cervical cancer via downregulating miR-223 and subsequently targeting EPB41L3. CONCLUSION: The study clarifies that HDAC10 inhibits cervical cancer by downregulating miR-223 and subsequently targeting EPB41L3 expression, which might provide a new insight for management upon cervical cancer and precancer lesions.

Incorporating productivity loss in health economic evaluations: a review of guidelines and practices worldwide for research agenda in China.

INTRODUCTION: Productivity loss may contribute to a large proportion of costs of health conditions in an economic evaluation from a societal perspective, but there is currently a lack of methodological consensus on how productivity loss should be measured and valued. Despite the research progress surrounding this issue in other countries, it has been rarely discussed in China. METHODS: We reviewed the official guidelines on economic evaluations in different countries and regions and screened the literature to summarise the extent to which productivity loss was incorporated in economic evaluations and the underlying methodological challenges. RESULTS: A total of 48 guidelines from 46 countries/regions were included. Although 32 (67%) guidelines recommend excluding productivity loss in the base case analysis, 23 (48%) guidelines recommend including productivity loss in the base case or additional analyses. Through a review of systematic reviews and the economic evaluation studies included in these reviews, we found that the average probability of incorporating productivity loss in an economic evaluation was 10.2%. Among the economic evaluations (n=478) that explicitly considered productivity loss, most (n=455) considered losses from paid work, while only a few studies (n=23) considered unpaid work losses. Recognising the existing methodological challenges and the specific context of China, we proposed a practical research agenda and a disease list for progress on this topic, including the development of the disease list comprehensively consisting of health conditions where the productivity loss should be incorporated into economic evaluations. CONCLUSION: An increasing number of guidelines recommend the inclusion of productivity loss in the base case or additional analyses of economic evaluation. We optimistically expect that more Chinese researchers notice the importance of incorporating productivity loss in economic evaluations and anticipate guidelines that may be suitable for Chinese practitioners and decision-makers that facilitate the advancement of research on productivity loss measurement and valuation.

Association between short-term exposure to ambient air pollution and heart failure: An updated systematic review and meta-analysis of more than 7 million participants.

Introduction: Exposure to air pollution has been linked to the mortality of heart failure. In this study, we sought to update the existing systematic review and meta-analysis, published in 2013, to further assess the association between air pollution and acute decompensated heart failure, including hospitalization and heart failure mortality. Methods: PubMed, Web of Science, EMBASE, and OVID databases were systematically searched till April 2022. We enrolled the studies regarding air pollution exposure and heart failure and extracted the original data to combine and obtain an overall risk estimate for each pollutant. Results: We analyzed 51 studies and 7,555,442 patients. Our results indicated that heart failure hospitalization or death was associated with increases in carbon monoxide (3.46% per 1 part per million; 95% CI 1.0233-1.046, P < 0.001), sulfur dioxide (2.20% per 10 parts per billion; 95% CI 1.0106-1.0335, P < 0.001), nitrogen dioxide (2.07% per 10 parts per billion; 95% CI 1.0106-1.0335, P < 0.001), and ozone (0.95% per 10 parts per billion; 95% CI 1.0024-1.0166, P < 0.001) concentrations. Increases in particulate matter concentration were related to heart failure hospitalization or death (PM2.5 1.29% per 10 µg/m3, 95% CI 1.0093-1.0165, P < 0.001; PM10 1.30% per 10 µg/m3, 95% CI 1.0102-1.0157, P < 0.001). Conclusion: The increase in the concentration of all pollutants, including gases (carbon monoxide, sulfur dioxide, nitrogen dioxide, ozone) and particulate matter [(PM2.5), (PM10)], is positively correlated with hospitalization rates and mortality of heart failure. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021256241.

Evaluation of a methylation classifier for predicting pre-cancer lesion among women with abnormal results between HPV16/18 and cytology.

BACKGROUND: Although HPV testing and cytology detection are successful for cervical screening in China, additional procedures are urgently required to avoid misdiagnosis and overtreatment. In this multicenter study, we collected cervical samples during screening in clinics. A total of 588 women with HPV16/18+ and/or cytology result ≥HSIL+ (high-grade squamous intraepithelial lesion or worse) were referred to colposcopy for pathological diagnosis. Methylation of S5 was quantified by pyrosequencing. RESULTS: The S5 classifier separates women with ≥HSIL+ from

Clinical outcomes and safety of apatinib monotherapy in the treatment of patients with advanced epithelial ovarian carcinoma who progressed after standard regimens and the analysis of the VEGFR2 polymorphism.

The aims of the present study were to investigate the clinical outcomes and safety of apatinib monotherapy in the treatment of patients with advanced epithelial ovarian carcinoma (EOC) who have progressed after standard regimens, and to analyze the vascular endothelial growth factor receptor 2 (VEGFR2) rs2071559 polymorphism. A total of 118 patients with advanced EOC who received apatinib treatment were included in the study. Tumor response was evaluated using progression-free survival (PFS) and overall survival (OS) time, and safety data were documented. Additionally, peripheral blood and peripheral blood mononuclear cell (PBMC) specimens from the patients with EOC were collected to perform the genotyping of genetic polymorphism and assess the mRNA expression of VEGFR2, respectively. The objective response rate across the 118 patients with advanced EOC was 38.98%, the disease control rate was 63.56%, the median PFS time was 4.65 months and the median OS time was 15.10 months. Regarding the polymorphism analysis, the prevalence of rs2071559 in VEGFR2 among the 118 patients with advanced EOC was recorded as the TT genotype in 72 cases (61.02%), TC genotype in 41 cases (34.75%) and CC genotype in 5 cases (4.23%), and the minor allele frequency of rs2071559 was 0.22. The distribution of the three genotypes was in accordance with the Hardy-Weinberg equilibrium (P=0.781). TC and CC genotypes were merged in the subsequent analysis. The prognosis analyses suggested that the median PFS time of patients with the TC/CC genotype and the TT genotype was 3.10 and 5.40 months, respectively (P=0.015). Moreover, the median OS time of the two genotypes was 12.60 and 17.50 months, respectively (P=0.009). However, no association was noted between genotype status of the polymorphism and adverse reactions. Additionally, the mRNA expression analysis indicated that the mRNA expression levels of VEGFR2 in PBMC specimens were significantly different between TT and TC/CC genotypes (P<0.001). The present study suggested that the clinical outcomes of patients with advanced EOC, who progressed after standard regimens and received apatinib treatment, might be influenced by the VEGFR2 rs2071559 polymorphism.

Bis[mu(3)-cis-N-(2-aminopropyl)-N'-(2-carboxylatophenyl)oxamidato(3-)]bis(2,2'-bipyridine)dichloridotetracopper(II) dihydrate.

The title complex, bis[mu(3)-cis-N-(2-aminopropyl)-N'-(2-carboxylatophenyl)oxamidato(3-)]-1:2:4kappa(7)N,N',N'',O:O',O'':O''';2:3:4kappa(7)O''':N,N',N'',O:O',O''-bis(2,2'-bipyridine)-2kappa(2)N,N';4kappa(2)N,N'-dichlorido-1kappaCl,3kappaCl-tetracopper(II) dihydrate, [Cu(4)(C(12)H(12)N(3)O(4))(2)Cl(2)(C(10)H(8)N(2))(2)].2H(2)O, consists of a neutral cyclic tetracopper(II) system having an embedded centre of inversion and two solvent water molecules. The coordination of each Cu(II) atom is square-pyramidal. The separations of Cu(II) atoms bridged by cis-N-(2-aminopropyl)-N'-(2-carboxylatophenyl)oxamidate(3-) and carboxyl groups are 5.2096 (4) and 5.1961 (5) A, respectively. A three-dimensional supramolecular structure involving hydrogen bonding and aromatic stacking is observed.

[Analysis on the origin and development of elements of reinforcing and reducing needling techniques].

Reinforcing and reducing needling manipulations are important factors affecting clinical therapeutic effect. In the present paper, the relevant elements of the reinforcing and reducing techniques of acupuncture needle including the left- and right-ward twirling, gender, needling at the left and right, front and back parts of the body, needling along or against the running course of the meridian, and their origin and development recorded in ancient Chinese medical books were collected and sorted out, followed by analysis on the understandings of Chinese ancient medical practitioners about them. Results show that the right- or left-ward twirling of needles, gender, and needling at the right or left part, the front or the back part of the body of patients are not the core components of the reinforcing and reducing techniques. Of the three stimulus parameters of needling, named amplitude, frequency and duration which are frequently researched at present, only the duration of single twirling (frequency) was highly noted in GAO Wu's book Zhenjiu Juying (A Collection of Gems in Acupuncture and Moxibustion). It is worthy of being studied in the further. Regarding the stimulation intensity of acupuncture involving the identification of reinforcing or reducing manipulations, the factors influencing the patients' feelings of needling intensity of acupuncture should be studied at the same time.

[The origin, development and mechanisms of special acupuncture needle tools for cutaneous region].

In this paper, we expound the origin and development of special acupuncture needle tools for cutaneous region, and discuss its mechanisms from modern medical theory. By consulting related acupuncture books and literature and in combination with needles used in clinical practice, we conclude that acupuncture needle tools can be divided into skin massage needle (digital pressing, spoon needle, etc.), cutaneous pricking blood needle (shear needle, three-edged needle, plum blossom needle, etc.), subcutaneous shallow puncture needle (intradermal needle, superficial needle, subcutaneous in-dwelling needle), etc. The skin-brain axis is the core of skin stimulation therapy. Mechanical pressure exerted on the skin surface induced by acupuncture stimulation or pressing, microcirculation changes and drug superposition are probably the underlying mechanisms of special skin acupuncture needle tools for treatment of various clinical disorders.

[Summary and core technique on the origin and evolution of reinforcing-reducing manipulation achieved by lifting and thrusting the needle].

By analyzing the evolution of reinforcing-reducing manipulation achieved by lifting and thrusting the needle recorded in ancient literature of traditional Chinese medicine, it is found that the main contents of reinforcing-reducing manipulation by lifting and thrusting the needle include manipulating speed change, manual amplitude, insertion layer, gender, the direction to the acupuncture receiver, forenoon and afternoon and relevant quantity. Among them, gender, the direction to the acupuncture receiver, forenoon and afternoon and relevant quantity are the unnecessary parameters, while the manipulating speed change, manual amplitude and insertion layer are the indispensable parameters. The manipulating speed change is the core of the necessary parameters for the reinforcing-reducing manipulation achieved by lifting and thrusting the needle. Combined with the manual amplitude, the manipulating speed of needle determines the volume of needling stimulation. The insertion layer is decided on the base of the clinical demand. In the core technique of reinforcing-reducing manipulation by lifting and thrusting the needle, the reinforcing is achieved by thrusting the needle forcefully and quickly and then lifting the needle body slowly and evenly back to the original layer. The reducing is achieved by lifting the needle forcefully and quickly and then thrusting the needle body slowly and evenly back to the original layer. The manipulating speed and manual amplitude of needling are the parameters to quantize acupuncture manipulation. In association with the acupuncture effects in human body, these parameters contribute to the interpretation of the dose-effect relationship of acupuncture and the improvement of clinical effects.

Metabonomics delineates allergic reactions induced by Shuang-huang-lian injection in rats using ultra performance liquid chromatography-mass spectrometry.

Shuang-huang-lian Injection (SHLI) is the first successfully developed drug from traditional Chinese medicine (TCM) powder for injection, since its use for the treatment of acute respiratory tract infection, pneumonia, influenza, etc. At the same time, its allergic reactions have also emerged, which limits clinical applications. However, few scholars pay attention to the mechanism of allergic reactions. In this present study, metabonomics technology was used to explore the changes in endogenous metabolites in urine of the rat model of SHLI induced allergic reaction; we and analyzed the metabolites, metabolic pathway, and the mechanism which were closely related to the allergic reactions. The levels of serum histamine and tryptase were examined and changes in histomorphology were also observed. Based on the UPLC-Q-TOF/MS metabonomics, we carried out the pattern recognition analysis, selected potential biomarkers associated with allergic reactions, and explored the pathological mechanism for SHLI induced allergic reaction, which laid the foundation for the safety research of SHLI. Our results showed that SHLI increased the levels of serum histamine and tryptase in rats with allergic reaction; we determined 15 biomarkers in rat allergic reaction model induced by SHLI and found multiple metabolic pathways involved, such as metabolism of linolenic acid, phenylalanine, amino acid, 2-oxo acid, and purine and other metabolic pathways.

Association of HSP90B1 genetic polymorphisms with efficacy of glucocorticoids and improvement of HRQoL in systemic lupus erythematosus patients from Anhui Province.

Objective: The aim of this study was to investigate the associations between HSP90B1 gene polymorphisms and the efficacy of glucocorticoids (GCs) and the improvement of health-related quality of life (HRQoL) in Anhui patients with systemic lupus erythematosus (SLE). Method: A total of 305 patients with SLE were recruited to the study. These patients were treated with GCs for 12 weeks and classified into two groups (sensitivity and insensitivity) according to the response to GCs measured by the scores on SLE disease activity index (SLEDAI). The HRQoL of SLE patients were evaluated by 36-item Short Form Health Survey (SF-36) at baseline and 12 weeks respectively. HapMap database and Haploview software were used to select HSP90B1 gene tag single nucleotide polymorphisms (SNPs). Benjamini & Hochberg (BH) method based on false discovery rate (FDR) was used for multiple testing correction. Results: A total of 291 patients were included in final data analysis with 14 patients excluded due to loss to follow-up. Among these patients, 160 patients were sensitive to GCs and 131 patients were insensitive to GCs. Twelve tag SNPs of HSP90B1 gene were selected. The rs12426382 polymorphism was associated with the efficacy of GCs (dominant model: crude OR=0.514, 95% CI=0.321-0.824, P=0.006; adjusted OR=0.513, 95% CI=0.317-0.831, P=0.007). After BH correction, there was no association between rs12426382 polymorphism and efficacy of GCs (PBH =0.084). In haplotype analysis, the haplotype CCCGAACATCCC (OR=2.273, 95% CI=1.248-4.139, P=0.006) and CTGGGACGTTC (OR=0.436, 95% CI=0.208-0.916, P=0.025) showed significant associations with the efficacy of GCs. After corrected by BH method, CCCGAACATCCC was still associated with the efficacy of GCs (PBH =0.048). The rs3794241, rs1165681, rs2722188, rs3794240 and rs10861147 polymorphisms were associated with the improvement of HRQoL among SLE patients (P < 0.05). But no association existed after the correction of BH method (P > 0.05). Conclusions: The results of this study demonstrated that HSP90B1 genetic polymorphisms might be associated with the efficacy of GCs, but not associated with the improvement of HRQoL in Anhui population with SLE.

Single nucleotide polymorphisms of HSP90AA1 gene influence response of SLE patients to glucocorticoids treatment.

Heat shock protein 90 (HSP90) is an important glucocorticoid receptor (GR) chaperone protein, and is supposed to be the key factor in regulating glucocorticoids (GCs) effects. The aim of the present study was to explore whether single nucleotide polymorphisms (SNPs) within HSP90AA1 gene affect the response of systemic lupus erythematosus (SLE) patients to GCs treatment. Two hundred and forty-five SLE patients were treated with GCs (prednisone) for 12 weeks. SLE disease activity index (SLEDAI) was used to assess the response of SLE patients to GCs treatment, and patients were classified into sensitive group and insensitive group. HapMap database and Haploview software were used to select tag SNPs. Tag SNPs were genotyped by using multiplex SNaPshot method. Univariate and multivariate logistic regression analyses were used to discriminate the impact of SNPs of HSP90AA1 gene on the response of SLE patients to GCs treatment. Two hundred and thirty three SLE patients finished the 12-week follow-up. Of these patients, 128 patients were included in sensitive group, and 105 patients were included in insensitive group. Seven tag SNPs were selected within HSP90AA1 gene. We detected significant associations for rs7160651 (dominant model: crude OR 0.514, 95 % CI 0.297-0.890, P = 0.018; adjusted OR 0.518, 95 % CI 0.293-0.916, P = 0.024), rs10873531 (dominant model: crude OR 0.516, 95 % CI 0.305-0.876, P = 0.014; adjusted OR 0.522, 95 % CI 0.304-0.898, P = 0.019) and rs2298877 (dominant model: crude OR 0.543, 95 % CI 0.317-0.928, P = 0.026, adjusted OR 0.558, 95 % CI 0.323-0.967, P = 0.037) polymorphisms, but not for other polymorphisms (P > 0.05). The present study demonstrates that HSP90AA1 gene SNPs may affect the response of SLE patients to GCs treatment.

Glucocorticoid receptor genetic polymorphisms is associated with improvement of health-related quality of life in Chinese population with systemic lupus erythematosus.

In our previous study, we found that glucocorticoid receptor (GR) gene genetic polymorphisms may play a major role in the efficacy of glucocorticoids (GCs) in Chinese systemic lupus erythematosus (SLE) patients. The aim of this study is to explore the association of GR gene genetic polymorphisms and improvement of health-related quality of life (HRQOL) in Chinese SLE patients treated with GCs. A total of 195 Chinese SLE patients were treated with GCs for 12 weeks. The HRQOL of patients was measured with the Medical Outcomes Study Short Form-36 (SF-36) at baseline and 12 weeks. Polymorphisms of GR gene were genotyped by using multiplex SNaPshot method. One hundred eighty-four patients (94.36 %) completed the 12-week follow-up. Twenty-three single-nucleotide polymorphisms of GR gene were genotyped. There was a significant association between rs10482672 polymorphism and improvement in physical function (P = 0.043), general health (P = 0.024), and social function (P = 0.013). The rs12656106 polymorphism was associated with improvement in the total score of SF-36 (P = 0.014), physical function (P = 0.013), general health (P = 0.010), vitality (P = 0.015), social function (P = 0.004), physical component summary (P = 0.016), and mental component summary (P = 0.014). The rs4912905 polymorphism was associated with improvement in bodily pain (P = 0.040) and general health (P = 0.038). The rs4912911 polymorphism was associated with improvement in general health (P = 0.026) and vitality (P = 0.027). The rs4986593 polymorphism was associated with improvement in bodily pain (P = 0.034). The rs7719514 polymorphism was associated with improvement in vitality (P = 0.002) and mental component summary (P = 0.041). We also found a significant association between rs9324924 polymorphism and improvement in physical function (P = 0.040), bodily pain (P = 0.007), and general health (P = 0.019). These results indicate that there may be an association of GR gene rs10482672, rs12656106, rs4912905, rs4912911, rs4986593, rs7719514, and rs9324924 polymorphisms with improvement of HRQOL in Chinese SLE patients treated with GCs.