Vaginal microbiome differences between patients with adenomyosis with different menstrual cycles and healthy controls.

BACKGROUND: Adenomyosis is a commonly observed benign gynecological disease that affects the quality of life and social psychology of women of childbearing age. However, because of the unknown etiology and incidence of adenomyosis, its pathophysiological mechanism remains unclear; further, because no noninvasive, accurate, and individualized diagnostic methods are available, treatment and efficacy evaluations are limited. Notably, the interaction between the changes in the microecological environment of the female reproductive tract and human immunity, endocrine, and other links leads to the occurrence and development of diseases. In addition, the vaginal microbiome differs in different menstrual cycles; therefore, assessing the differences between the microbiomes of patients with adenomyosis and healthy individuals in different menstrual cycles will improve the understanding of the disease and provide references for the search for noninvasive diagnosis and individualized precision treatment of adenomyosis. This study aimed to explored the data of individuals in different menstrual cycles. RESULTS: Differences in the vaginal microbiome between patients with adenomyosis and healthy individuals were observed. At phylum level, the relative abundance of Firmicutes in the adenomyosis group was higher than that in the control group, which contributed the most to the species difference between the two groups. At the genus level, Lactobacillus was the most dominant in both groups, Alpha-diversity analysis showed significant differences in the adenomyosis and control group during luteal phase (Shannon index, p = 0.0087; Simpson index, p = 0.0056). Beta-diversity index was significantly different between the two groups (p = 0.018). However, based on Weighted Unifrac analysis, significant differences were only observed throughout the luteal phase (p = 0.0146). Within the adenomyosis group, differences between women with different menstrual cycles were also observed. Finally, 50 possible biomarkers including were screened and predicted based on the random forest analyse. CONCLUSIONS: The vaginal microbiome of patients with adenomyosis and healthy individuals differed during menstrual periods, especially during the luteal phase. These findings facilitate the search for specific biological markers within a limited range and provide a more accurate, objective, and individualized diagnostic and therapeutic evaluation method for patients with adenomyosis, compared to what is currently available.

Efficacy and uterine bleeding patterns in initiating goserelin therapy during different menstrual phases in patients with adenomyosis: a prospective cohort study.

OBJECTIVE: We carried out this study to explore the possibility of initiating goserelin therapy during the non-menstrual period in patients diagnosed with adenomyosis. METHODS: 115 premenopausal adenomyosis patients were enrolled and divided into three groups based on their menstrual cycle phase during the initial outpatient visit: menstrual, follicular, and luteal. Each received a 3.6 mg subcutaneous dose of goserelin monthly for three months. The endpoints encompassed alterations in uterine volume, dysmenorrhea Numerical Rating Scale (NRS) score, CA125 level, hemoglobin (HGB) after a 12-week treatment course, and the occurrence and duration of uterine hemorrhage during the first treatment cycle. RESULTS: Analysis revealed that the timing of goserelin therapy initiation in the menstrual cycle did not significantly impact its effectiveness in reducing uterine size, alleviating pain, lowering CA125 levels, or improving hemoglobin concentrations. However, patients starting treatment during the luteal phase experienced increased uterine bleeding (reference: menstrual period, OR = 4.33, 95% CI 1.23-15.25, p = .023). CONCLUSIONS: The results suggested non-inferiority of goserelin therapy initiated during the non-menstrual period, but the uterine bleeding rate was higher in the luteal phase group. Therefore, goserelin treatment for outpatient adenomyosis patients should not be limited to starting during the menstrual period; it can also be initiated outside the menstrual period, providing more convenience for patients as most consultations occur outside the menstrual period. However, the use of goserelin during the luteal phase should be avoided to reduce the risk of exacerbated bleeding, especially in anemic patients with heavy menstrual bleeding. This study highlights the importance of individualizing treatment initiation based on the patient's health profile to optimize therapeutic outcomes and minimize adverse effects. TRIAL REGISTRATION: ChiCTR2200059548.

Escherichia coli inhibits endometriosis by inducing M1 polarity of peritoneal macrophages and the IL-1 signaling pathway.

The development of endometriosis is closely linked to macrophages, and the type M1 macrophage has been hypothesized to play an inhibitory role in its progression. Escherichia coli induces macrophage polarization toward M1 in numerous diseases and differs in the reproductive tract of patients with and without endometriosis; however, its specific role in endometriosis development remains unknown. Therefore, in this study, E. coli was selected as a stimulator to induce macrophages, and its effects on the growth of endometriosis lesions in vitro and in vivo were investigated using C57BL/6N female mice and endometrial cells. It was revealed that E. coli inhibited the migration and proliferation of co-cultured endometrial cells by IL-1 in vitro and prevented the growth of lesions and induced macrophage polarization toward M1 in vivo. However, this change was counteracted by C-C motif chemokine receptor 2 inhibitors, suggesting that it was associated with bone marrow-derived macrophages. Overall, the presence of E. coli in the abdominal cavity may be a protective factor for endometriosis.

Endometrial stromal cell autophagy-dependent ferroptosis caused by iron overload in ovarian endometriosis is inhibited by the ATF4-xCT pathway.

Ferroptosis is an iron-dependent programmed cell death process characterized by the accumulation of lethal oxidative damage. Localized iron overload is a unique clinical phenomenon in ovarian endometriosis (EM). However, the role and mechanism of ferroptosis in the course of ovarian EM remain unclear. Traditionally, autophagy promotes cell survival. However, a growing body of research suggests that autophagy promotes ferroptosis under certain conditions. This study aimed to clarify the status of ferroptosis in ovarian EM and explore the mechanism(s) by which iron overload causes ferroptosis and ectopic endometrial resistance to ferroptosis in human. The results showed increased levels of iron and reactive oxygen species in ectopic endometrial stromal cells (ESCs). Some ferroptosis and autophagy proteins in the ectopic tissues differed from those in the eutopic endometrium. In vitro, iron overload caused decreased cellular activity, increased lipid peroxidation levels, and mitochondrial morphological changes, whereas ferroptosis inhibitors alleviated these phenomena, illustrating activated ferroptosis. Iron overload increased autophagy, and ferroptosis caused by iron overload was inhibited by autophagy inhibitors, indicating that ferroptosis caused by iron overload was autophagy-dependent. We also confirmed the effect of iron overload and autophagy on lesion growth in vivo by constructing a mouse EM model; the results were consistent with those of the in vitro experiments of human tissue and endometrial stomal cells. However, ectopic lesions in patients can resist ferroptosis caused by iron overload, which can promote cystine/glutamate transporter hyperexpression by highly expressing activating transcription factor 4 (ATF4). In summary, local iron overload in ovarian EM can activate autophagy-related ferroptosis in ESCs, and ectopic lesions grow in a high-iron environment via ATF4-xCT while resisting ferroptosis. The effects of iron overload on other cells in the EM environment require further study. This study deepens our understanding of the role of ferroptosis in ovarian EM.

Iron deposition in ovarian endometriosis evaluated by magnetic resonance imaging R2* correlates with ovarian function.

RESEARCH QUESTION: Does iron overload in patients with endometriosis affect ovarian function? Can a method be developed to visually reflect this? DESIGN: Magnetic resonance imaging (MRI) R2* was used to evaluate the correlation between iron deposition of ovarian and anti-Müllerian hormone (AMH) in patients with endometriosis. All patients underwent T2* MRI scanning. Serum AMH levels were measured preoperatively. The area of focal iron deposition, iron content of the cystic fluid and AMH levels between the endometriosis and control groups were compared using non-parametric tests. The effects of iron overload on AMH secretion in mouse ovarian granulosa cells were investigated by adding different concentrations of ferric citrate to the medium. RESULTS: A significant difference was found between endometriosis and control groups in area of iron deposition (P < 0.0001), cystic fluid iron content (P < 0.0001), R2* of lesions (P < 0.0001) and R2* of the cystic fluid (P < 0.0001). Negative correlations were found between serum AMH levels and R2* of cystic lesions in patients with endometriosis aged 18-35 years (rs = -0.6484, P < 0.0001), and between serum AMH levels and R2* of cystic fluid (rs = -0.5074, P = 0.0050). Transcription level (P < 0.0005) and secretion level (P < 0.005) of AMH significantly decreased with the increase in iron exposure. CONCLUSION: Iron deposits can impair ovarian function, which is reflected in MRI R2*. Serum AMH levels and R2* of cystic lesions or fluid in patients aged 18-35 years had a negative correlation with endometriosis. R2* can be used to reflect the changes of ovarian function caused by iron deposition.

Clinical efficacy and safety of trimonthly administration of goserelin acetate 10.8 mg in premenopausal Chinese females with symptomatic adenomyosis: a prospective cohort study.

OBJECTIVE: This prospective cohort study aimed to compare the clinical efficacy and safety of goserelin 10.8 mg administered trimonthly with goserelin 3.6 mg administered monthly in premenopausal females with symptomatic adenomyosis. METHODS: We recruited 139 premenopausal females with adenomyosis who complained of dysmenorrhea and/or menorrhagia. The first group (n = 70) received a single subcutaneous injection of goserelin 10.8 mg, and the second group (n = 69) received monthly subcutaneous goserelin 3.6 mg administered for 3 months. Follow-up was performed at the outpatient department after 12 weeks. RESULTS: Ultimately, 130 patients completed the study, including 68 and 62 patients in the goserelin 10.8 mg (n = 70) and 3.6 mg (n = 69) groups, respectively. We observed a significant decrease in the dysmenorrhea (NRS) score, uterine volume, and cancer antigen 125 (CA125) levels, and a significant increase in hemoglobin (HGB) levels in both treatment groups. There was no significant difference between the two groups. The sum of the adverse event scores was slightly higher in the goserelin 3.6 mg than in the 10.8 mg group. CONCLUSIONS: The clinical efficacy of trimonthly administration of goserelin 10.8 mg was equivalent to monthly 3.6 mg dosing and was non-inferior regarding safety and tolerability. Hence, it can be a more cost-effective and convenient alternative treatment option in premenopausal females with symptomatic adenomyosis. TRIAL REGISTRATION: ChiCTR2200059548.

Macrophage-associated immune checkpoint CD47 blocking ameliorates endometriosis.

Peritoneal macrophages play a significant role in the progression of endometriosis (EM), but their functional differentiation is still unclear, and their phagocytic ability is weak. CD47-signal-regulated protein α (SIRPα) and PD-L1-PD-1 are considered immune checkpoints associated with macrophage phagocytosis. A specific blockade of these two pathways had been shown to increase the phagocytic clearance of cancer cells by macrophages in most cancers. We hypothesized that targeting CD47/PD-L1 in EM could improve the phagocytosis of macrophages, thereby delaying the progression of EM. From localization to quantification, from mRNA to protein, we comprehensively evaluated the expression of CD47 and PD-L1 in EM. We demonstrated that the CD47 expression in ectopic endometrium from patients with EM was significantly increased, but PD-L1 was not. We performed direct co-culture experiments of endometrial stromal cells with macrophages in vitro and in vivo to assess whether ectopic endometrial stromal cells escape macrophage phagocytosis through the CD47-SIRPα signaling pathway. The results showed that targeting CD47 increased the phagocytic capacity of macrophages. Interestingly, we also found that the reduction of CD47 expression promoted apoptosis of endometrial stromal cells. In conclusion, these data suggested that targeting CD47 can effectively target ectopic endometrial stromal cells through a dual mechanism of increased phagocytosis of macrophages and induced apoptosis of ectopic endometrial stromal cells. Thus, immunotherapy based on the CD47-SIRPα signaling pathway has some potential in treating EM, but further mechanistic studies are needed to explore more effective and specific antibodies.

Theoretical study of point defects on transport properties in metallic interconnections.

During the line width reduction, electron scattering caused by various defects in metal interconnects increases dramatically, which causes leakage or short circuit problems in the device, reducing device performance and reliability. Point defects are one of the important factors. Here, using density functional theory and non-equilibrium Green's function methods, we systematically study the effects of point defects on the transport properties of metals Al, Cu, Ag, Ir, Rh, and Ru, namely vacancy defects and interstitial doping of C atom. The results show that the conductivity of all systems decreases compared to perfect systems, because defects cause unnecessary electron scattering. Since the orbital hybridization of the C atom with the Al, Cu and Ag atoms is stronger than that metals Ir, Rh and Ru, the doping of C atom significantly reduces the conductivity of metals Al, Cu and Ag compared to vacancy defects. In contrast, vacancy defects have a greater impact than doping on the transport properties of metals Ir, Rh and Ru, which is mainly attributed to the larger charge transfer of the host atoms around the vacancies caused by lattice distortion. In addition, metal Rh exhibits excellent conductivity in all systems. Therefore, in order to optimize the transport properties of interconnect metals, our work points out that the doping of impurity atoms should be avoided for metals Al, Cu and Ag, while the presence of vacancy defects should be avoided for metals Ir, Rh and Ru, and Rh may be an excellent candidate material for future metal interconnects.

A Multicriteria Approach for Measuring Employee Well-Being.

This paper proposes that employee well-being includes four dimensions: job satisfaction, life satisfaction, positive affect, and negative affect. Each dimension is interdependent and correlated. Therefore, the measurement of employee well-being is complicated and fuzzy. This study aims to treat the measurement of employee well-being as a fuzzy problem, construct a measurement model from the perspective of multi-criteria decision making, and establish the preference relationship between indicators through fuzzy measure and Choquet integral. Applying multiple linear regression analysis and the heuristic least mean squares method, the main findings are as follows: (1) It is inappropriate to use job satisfaction as a substitute for measuring employee well-being, as the weight of job satisfaction is the lowest among the four dimensions. (2) Employee well-being is also largely reflected in their overall satisfaction with life because life satisfaction is the most heavily weighted. (3) Employee well-being needs to consider the emotion-related indicators and satisfaction-related indicators comprehensively because fuzzy analysis proves that their relationship is redundant. Finally, the practical implications of these findings and future research directions are discussed.

Evolutionary game analysis between employees and employers about working overtime from the perspective of information asymmetry.

BACKGROUND: Overtime is an international phenomenon, especially in some Chinese Internet technology companies, the 996 work regime is a common corporate atmosphere. This paper holds that overtime work is the result of a long-term dynamic game between employees and employers. In such a dynamic evolution process, employers and employees both cooperate and conflict, they will choose a strategy conducive to their own development through long-term learning and improvement. METHODS: Based on the evolutionary game theory and principal-agent theory, this paper constructs a [Formula: see text] evolutionary game matrix. The strategies of employees can be divided into voluntary overtime and involuntary overtime, while the strategies of employers can be divided into providing overtime pay and not providing overtime pay. The stability of the system is related to four parameters: resource consumption, information asymmetry coefficient, trust coefficient, and moral hazard coefficient. RESULTS: Through an in-depth study of the model and data simulation, the system has five equilibrium points, an ESS point, and a saddle point in any case. Accordingly, we put forward two theorems and three propositions, which are verified not only theoretically but also by data simulation. Besides, the strategies of the employees and the employers will evolve from the initial state to (Involuntarily, Not pay) or (Voluntarily, Pay) under different situations. This is closely related to the initial parameters of the evolutionary game model and the payment matrix. CONCLUSIONS: By summarizing the influence of each parameter on the evolutionary path, we believe that fairness and information equivalence between employees and employers can effectively promote both parties to reach the Pareto optimal state. In other words, employees and employers need to communicate and share information promptly to ensure the unity of information acquired by each other and achieve a win-win situation. This paper contributes to providing theoretical guidance and practical enlightenment for organizations to manage employees' overtime behavior scientifically and improve their work psychology reasonably.

A Bibliometric Analysis of Knowledge-Hiding Research.

Knowledge hiding, defined as an intentional attempt to conceal requested knowledge, has become a hot topic in management and psychology in the last decade. Emerging research has suggested that knowledge hiding is not simply the opposite of knowledge sharing, such that it is crucial to clarify the concept, explore the research progress and development trend of knowledge hiding. Based on 243 relevant articles, a bibliometric analysis of knowledge-hiding research is presented via descriptive, keyword and citation analysis. Results reveal that knowledge-hiding research, mainly focusing on the disciplines of management, business and psychology, is currently in a period of rapid growth, especially in the past two or three years. The systematic review of knowledge-hiding research enables us intuitively to obtain a panoramic view, including publication performance, thematic evolution and most influential topics of the field via a set of science maps, enabling future authors to investigate knowledge hiding and focus their research more effectively.

Deficiency of MST1 in endometriosis related peritoneal macrophages promoted the autophagy of ectopic endometrial stromal cells by IL-10.

Changes in the function of peritoneal macrophages contribute to the homeostasis of the peritoneal immune microenvironment in endometriosis. The mechanism by which ectopic tissues escape phagocytic clearance by macrophages to achieve ectopic colonization and proliferation is unknown. The expression of CD163 in peritoneal macrophages in patients with endometriosis is increased, with the overexpression of MAPK, which can promote the M2-type polarization of macrophages and reduce their ability to phagocytose ectopic endometrial cells. As an upstream regulator of MAPK, MST1 expression is deficient in peritoneal macrophages of patients with endometriosis. This process is regulated by miR-887-5p, a noncoding RNA targeting MST1. Moreover, MST1-knockout macrophages secrete anti-inflammatory factor IL-10, which promotes autophagy of ectopic endometrial stromal cells. These results suggest that MST1 deficient macrophages may accelerate the autophagy of ectopic endometrium via IL-10 which was regulated by miR-887-5p.

Brain Morphological and Functional Changes in Adenomyosis with Pain: A Resting State Functional Magnetic Resonance Imaging Study.

The absence of clinically objective methods to evaluate adenomyosis-associated pain and the poor understanding of its pathophysiology lead to treatment limitations. We conducted a resting-state functional magnetic resonance imaging study with 49 patients with pain-related adenomyosis and 30 pain-free controls to investigate brain morphological alterations and regional dysfunctions in patients with pain-related adenomyosis. These patients had significantly higher scores for anxiety and depression than the control group (p < 0.05). They also had a lower gray matter volume (GMV) in the bilateral insula, left angular gyrus, precuneus, left inferior temporal gyrus, and left postcentral gyrus (p < 0.05, AlphaSim corrected). Similarly, decreased voxel-mirrored homotopic connectivity was observed in the bilateral insula, posterior cingulate cortex, middle frontal gyrus, and postcentral gyrus in the adenomyosis patient group (p < 0.05, AlphaSim corrected). Regional homogeneity showed significant differences mainly in the bilateral cerebellum, left inferior frontal gyrus, medial prefrontal cortex, and posterior cingulate gyrus. Correlation analysis showed that the degree of depression in patients with adenomyosis was negatively correlated with the GMV of the left angular gyrus. The results show that these patients exhibited changes in multiple brain regions associated with pain as well as emotion perception and processing.

Incidence of malignancy in primary Sjogren's syndrome in a Chinese cohort.

OBJECTIVES: To evaluate the incidence of malignancies in a cohort of Chinese patients with primary Sjögren's syndrome (pSS) and to identify the risk factors of malignancy in pSS patients. METHODS: A retrospective analysis was carried out in 1320 pSS patients who were recruited in Peking Union Medical College Hospital from 1990 to 2005 and were followed up for an average of 4.4 years. Among them, 29 patients developed malignancies. Standardized incidence ratios (SIRs) were calculated along with 95% CIs. Clinical characteristics were compared between patients with and without malignancies, as well as patients with haematological and non-haematological tumours. RESULTS: Of the pSS patients, 2.2% developed malignancies during follow-up. Total SIR and SIR for lymphoma were 3.25 and 48.1, respectively. Different types of malignancy were observed including eight lymphomas, two myeloid myelomas and 19 solid tumours, which consisted of invasive thymoma, breast cancer, lung cancer, gastrointestinal adenocarcinoma, hepatoma, squamous cell carcinoma of tongue, uterine cervix cancer, renal carcinoma, thyroid carcinoma and mucoepidermoid carcinoma of parotid gland. Risk factor analysis showed that lymphadenopathy, enlargement of parotid glands, monoclonal immunoglobulin and absence of hypergammaglobulinaemia were correlated with malignancies. CONCLUSIONS: The current study confirms the increased incidence of lymphoma in Chinese patients with pSS, with the majority of B-cell non-Hodgkin's lymphoma. Associations between pSS and other malignant tumours such as myeloid myeloma, mouth cancer, breast cancer and thymoma need to be further observed.

Cadmium chloride enhances cisplatin sensitivity in osteosarcoma cells by reducing FOXM1 expression.

Osteosarcoma is a highly malignant disease and is associated with a poor patient prognosis and a high mortality rate. Disease prognosis significantly correlates with chemotherapeutic responses. Cadmium is a heavy metal with specific effects on bone, but its benefits for osteosarcoma treatment have not been characterized. In the present study, cadmium chloride was used to treat MG63 osteosarcoma cells, and their gene expression profiles were assessed by GeneChip technology. We found that forkhead box protein M1 (FOXM1) was downregulated by cadmium chloride, and lentiviral­mediated silencing of FOXM1 confirmed a role for this factor in the cisplatin resistance of MG63 cells. In nude mice, cadmium chloride enhanced the sensitivity of osteosarcoma to cisplatin, an effect mediated by FOXM1. Collectively, these data indicate that cadmium chloride can alter the sensitivity of osteosarcoma cells to cisplatin through FOXM1, highlighting it as a potential therapeutic target and prognostic factor for osteosarcoma.

Salt-Free Dyeing of Modified Cotton through Graft Polymerization with Highly Enhanced Dye Fixation and Good Strength Properties.

Modification of cotton fabric with 2-methacryloyloxyethyltrimethyl ammonium chloride (DMC) was achieved through free-radical initiated graft polymerization with K2S2O8/NaHSO3 as the initiator. Grafting of DMC was confirmed by ATR-IR of the modified cotton. The optimal grafting reaction conditions, including DMC dosage, mole ratio of initiator to DMC, temperature, and time, were determined by cation content and dye fixation results of the modified cotton. The modified fibers were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), and whiteness measurement. Salt-free dyeing of the modified cotton with commonly used C. I. Reactive Blue 19, C. I. Reactive Yellow 145, and C. I. Reactive Red 195 presented high fixation of 96.8%, 98.7%, and 97.3%, respectively. These results indicated that the modification is effective for changing the surface charge of the fiber and increasing the dye-fiber reactivity. The color fastness and strength property were still very satisfactory. With excellent properties, this dyeing method shows promise in real application for eliminating the usage of salt and reducing environmental pollution.

[A clinical analysis of primary Sjögren's syndrome with anticentromere antibodies].

OBJECTIVE: To investigate the clinical manifestations, immunological features and prognosis of primary Sjögren's syndrome (pSS) with anticentromere antibodies (ACA). METHODS: Sixty pSS patients with ACA in our hospital between 1985 and 2006 were screened retrospectively and compared with those without ACA. RESULTS: The mean age at the onset of pSS with ACA was higher than that of those without ACA [(48 +/- 11) yr vs (41 +/- 12) yr, P =0.000]. There was no difference in sex ratio, dry mouth, dry eyes and positive salivary gland biopsy between the two groups (P > 0.05). Compared with those without ACA, patients with ACA presented a higher prevalence of liver involvement (68.3% vs 37.0%, P = 0.000), while a lower prevalence of renal involvement (13.3% vs 30.9%, P = 0.009), neuropathy (1.7% vs 11.5%, P = 0.025) and hypergammaglobulinemia (20.8% vs 45.7%, P = 0.002). The difference was not significant between the two groups in Raynaud's phenomenon, articular involvement, myositis, hematologic involvement, lung involvement, and thyroiditis. While both groups showed the same prevalence of antinuclear antibody (ANA), the patterns of ANA-IF were different and the discrete speckled pattern was the most frequent in patients with ACA and occurred in 61.7%. Different from those without ACA, patients with ACA presented a lower prevalence of anti-SSA, anti-SSB, rheumatoid factor, and anti-U1RNP, while showed a higher prevalence of antimitochondrial antibodies (AMA) and AMA-M2. The most frequent cause of death was the complications associated with cirrhosis, notably bleeding varices (3/5 cases). CONCLUSION: Patients with ACA present a high risk of liver involvement. Because of the remarkable difference in the mean age of disease onset and also differences in systemic damage, immunological and antibody features, pSS with ACA may be a special subtype of pSS.

[Lung involvement of primary Sjögren's syndrome].

OBJECTIVE: To evaluate the incidence, clinical manifestations and immunological features of lung involvement in patients of primary Sjögren's syndrome (pSS). METHODS: Five hundred twenty-two patients with pSS in Peking Union Medical College Hospital between 1985 and 2005 were screened retrospectively for lung involvement by either the abnormalities of chest imaging, lung function or the pulmonary artery systolic pressure estimated by ultrasonic echocardiogram > or = 40 mm Hg (1 mm Hg = 0.133 kPa), excluding infections, chronic obstructive pulmonary disease, asthma, congenital heart disease, rheumatic heart disease and other diseases. The difference was compared between patients with and without lung involvement. All patients fulfilled the 2002 international classification (criteria) for pSS. RESULTS: (1) The incidence of lung involvement in pSS was 42.3% (221/522) and occurred from 0 to 384 months (median, 48 months) after onset, while 25.2% occurred before the diagnosis of pSS. Only 47.1% of the patients showed respiratory symptoms. The average age of onset was older in patients with lung involvement than in those without lung involvement [(43 +/- 13) yr vs (37 +/- 14) yr, t = -5.445, P = 0.000]. Incidences of dry mouth (89.6% vs 81.1%, chi2 = 7.145, P = 0.008), dry eyes (78.7% vs 66.4%, chi2 = 9.472, P = 0.002) and rampant caries (55.2% vs 42.2%, chi2 = 8.647, P = 0.003) were higher in patients with lung involvement than those without. There was no significant difference in sex ratio between the two groups. (2) Interstitial lung disease was the most common lung involvement and occurred in 23.2% of the patients. Pulmonary artery hypertension in 12.5%, multiple pulmonary bullae in 9.2%, pleural effusion in 6.0% and multiple pulmonary nodules in 5.6%. (3) The major histopathological patterns were nonspecific interstitial pneumonia (5/11 cases), lymphocytic interstitial pneumonia (3/11 cases). (4) Incidences of Ranaud' s phenomenon (26.7% vs 13.0%, chi2 = 15.77, P = 0.000 ), low-grade fever (20.4% vs 13.0%, chi2 = 5.175, P = 0.023), arthrosis (29.4% vs 21.6%, chi2 = 4.164, P = 0.041), anti-U1RNP (18.2% vs 11.2%, 2 = 5.069, P = 0.024) and hypergammaglobulinemia (51.6% vs 39.5%, chi2 = 6.597, P = 0.01) were higher in patients with lung involvement than in those without. The incidence of renal tubule acidosis was lower in patients with lung involvement than in those without (5.4% vs 12.6% chi2 = 7.616, P = 0.006). (5) The death incidence in pSS with pulmonary involvement was 5.5 times higher than in those without. The most frequent cause of death was infection (64.3%), especially pulmonary infection. CONCLUSION: Lung involvement in pSS is common. As it is an important factor related to the prognosis of this disease, chest X-ray, HRCT, lung function and ultrasonic echocardiogram after the diagnosis are suggested.

Characteristics and risk factors of pulmonary arterial hypertension in patients with primary Sjögren's syndrome.

AIM: To describe baseline characteristics of patients with primary Sjögren's syndrome (pSS) with right heart catheterization (RHC)-confirmed pulmonary arterial hypertension (PAH) and explore risk factors for PAH in pSS. METHODS: This case-control study included consecutive patients hospitalized with pSS-PAH from 2007 to 2015, and pSS patients without PAH (in a 4 : 1 ratio) as controls. All patients fulfilled the 2002 American-European Consensus Group classification criteria for pSS-PAH was defined according to RHC-based European Society of Cardiology/European Respiratory Society guidelines. Associated variables were analyzed by univariate binary logistic regression to identify possible risk factors for PAH. RESULTS: Twenty-nine patients with RHC-confirmed pSS-PAH were included (mean age at onset, 38.4 ± 8.3 years; mean pSS duration, 54.6 months). PAH was the initial manifestation of pSS in 12 patients (41.4%), and shortness of breath was the most common symptom (29/29, 100%). Mean pulmonary arterial pressure was 51.8 ± 10.0 mmHg, mean cardiac index was 2.3 ± 0.8 L/min/m2 , and mean pulmonary vascular resistance was 13.0 ± 6.0 Wood units in this group. Treatments included immunosuppressive agents (93.1%) and PAH-targeted therapies (86.2%). We identified four independent risk factors for PAH in pSS: Raynaud's phenomenon (odds ratio [OR] = 9.660, P = 0.000), rheumatoid factor ≥ 200 U/mL (OR = 6.691, P = 0.001), hepatic injury (OR = 3.284, P = 0.008) and pericardial effusion (OR = 3.279, P = 0.016). CONCLUSIONS: PAH can be the first manifestation of pSS. The pSS patients with Raynaud's phenomenon, high-titer rheumatoid factor, hepatic injury or pericardial effusion should be screened for PAH.

Clinical and prognostic characteristics of 573 cases of primary Sjögren's syndrome.

BACKGROUND: Primary Sjögren's syndrome (pSS) is one of the autoimmune diseases with high incidence. There were several clinical investigations in Caucasian but seldom in Chinese. The aim of this study was to compare the difference of clinical manifestations, immunological features and prognosis of pSS between Caucasian and Chinese pSS patients. METHODS: Five hundred and seventy-three patients who fulfilled the 2002 international classification (criteria) for pSS from Peking Union Medical College Hospital between 1985 and 2006 were screened retrospectively and compared with other populations. RESULTS: (1) The study consisted of 524 (91%) female and 49 (9%) male patients (female: male = 10.7:1). Mean age at the onset of the disease was (39.0 ± 13.7) years and in 169 (29.5%) patients the disease onset occurred before the age of 30 years. The average duration from disease onset to pSS diagnosis was 48 months (range, 1 - 552 months). It had been shortened during the recent five years. (2) Dry mouth (84.5%) and dry eyes (70.0%) were the most common symptoms, significantly lower than foreign patients (P = 0.000). Two hundred and seventy-two (47.5%) patients presented with rampant caries, 160 (27.9%) with parotidomegaly. The positivity of xerostomia, xerophthalmia and salivary gland biopsy were 91.9%, 94.8% and 90.7%, respectively. (3) Systemic involvement occurred in 91.4% patients. Compared with studies done outside China, higher prevalence of fever 41.0%, myositis 4.9%, pericardial effusion 14.8%, pulmonary involvement 42.3%, renal involvement 33.5%, thyroid involvement 32.7%, pancrease involvement 5.6% (P < 0.01) and lower prevalence of fatigue, lymphadenectasis and Raynaud's phenomenon (P < 0.01) were seen. (4) Risk factors of death include pulmonary artery hypertension, liver damage and interstitial lung disease. CONCLUSIONS: Chinese pSS differs significantly from the non-Chinese cases in terms of the age of onset, systemic involvement, autoantibodies and proportional mortality rate. Lung and liver damage were found to be the highest risk factors of the disease prognosis.