Coffee consumption might be associated with lower potential risk and severity of metabolic syndrome: national health and nutrition examination survey 2003-2018.

BACKGROUND: Metabolic syndrome (MetS) is a clinical syndrome characterized by multiple metabolic disorders and is a serious global health problem. The coffee effect, acting as one of the most prevalent beverages on metabolic syndrome, is debatable. METHODS: We included patients from the National Health and Nutrition Examination Survey 2003-2018 and used a comprehensive evaluation called the MetS z-score to assess the severity of metabolic syndrome. The relationship between coffee, decaffeinated coffee, tea, and MetS z-scores was explored using a weighted linear regression. We also divided the participants into metabolic and non-metabolic syndrome groups according to the NCEP/ATP III criteria for the subgroup analysis. RESULTS: A total of 14,504 participants were included in this study. The results demonstrated that drinking more than three cups of coffee daily was significantly linked to lower MetS z-scores (p < 0.001). Daily coffee consumption was also associated with lower BMI (p = 0.02), systolic blood pressure (p < 0.001), Homeostatic Model Assessment for Insulin Resistance (p < 0.001), and triglycerides (p < 0.001), while it was positively correlated with HDL-C (p = 0.001). Participants who consumed more than three cups of coffee daily had a lower MetS z-score in the MetS (p < 0.001) and non-MetS (p = 0.04) groups. CONCLUSION: This research indicates that coffee consumption is linked to MetS severity. However, decaffeinated coffee and tea intake were unrelated to MetS severity.

Association of the American Heart Association's new "Life's Essential 8" with all-cause mortality in patients with chronic kidney disease: a cohort study from the NHANES 2009-2016.

BACKGROUND: People with chronic kidney disease (CKD) are more likely to die prematurely, and this increased risk of death is primarily attributable to deaths from cardiovascular disease (CVD). We aim to investigate the relationship between Life's Essential 8 (LE8), a newly proposed cardiovascular health (CVH) measurement system, and all-cause mortality of CKD patients among US adults. METHODS: A total of 3,169 CKD patients aged 20 and older from the National Health and Nutritional Examination Survey in 2009-2016 were involved in this study. Participants were divided into low (0-49), moderate (50-79) and high (80-100) CVH groups according to LE8 score (range 0-100). The mortality was ascertained from the National Death Index. Cox proportional hazards regression and restricted cubic spline were used to investigate the relationship. RESULTS: Among the 3,169 CKD patients, the median age was 66.0 (25.0) years and 1,671 (52.7%) were female, and the median follow-up time was 6.00 years. The median LE8 score of the study cohort was 57.5 (19.4). CKD patients with low CVH, health behavior (HB) and health factors (HF) scores presented with higher all-cause mortality (both log-rank P-values < 0.001). After adjusted for multiple confounders, patients in higher CVH group had a lower risk of all-cause mortality, with a HR (95%CI) of 0.32 (0.19-0.55). Similar results were observed in high HB group [HR 0.36 (0.25-0.50)]. The restricted cubic spline showed a significant inverse relationship between LE8, HB and HF scores with CKD all-cause mortality, while the protective effect seemed weaker for HF score. Above results remained robust in the sensitivity analysis. Stronger inverse associations were revealed in middle-aged patients and patients with higher education levels. CONCLUSIONS: LE8 and its subscales scores were inversely associated with all-cause mortality in patients with CKD. Promoting CVH in CKD patients is a potential way to improve their long-term survival rate.

Assessment of the correlation between KAP scores regarding sugar-sweetened beverage consumption and hyperuricemia amongst Chinese young adults.

BACKGROUND: The prevalence of hyperuricemia in China has been consistently increasing, particularly among the younger generation. The excessive consumption of sugar-sweetened beverages is associated with hyperuricemia. This study examined the knowledge, attitudes, and practices (KAP) of Chinese young adults regarding sugar-sweetened beverage consumption and the correlation with hyperuricemia. METHODS: This cross-sectional investigation was conducted from June 28th, 2023, to July 21st, 2023, and enrolled Chinese young adults. Demographics and KAP were evaluated using a questionnaire (Cronbach's α = 0.787). Factors influencing KAP scores were analyzed using multivariable analyses. RESULTS: A total of 1288 valid questionnaires were analyzed. The median knowledge, attitude, and practice scores were 16 (12,19)/22, 22 (20,24)/30, and 27.5 (23,31.75)/40. The multivariable analysis showed that bachelor's/associate education (OR = 1.912, 95%CI: 1.128-3.239), white collar/employee (OR = 0.147, 95%CI: 0.105-0.206), educator (OR = 0.300, 95%CI: 0.174-0.518), healthcare worker (OR = 0.277, 95%CI: 0.188-0.407), not suffering from hyperuricemia (OR = 0.386, 95%CI: 0.253-0.590), and not having gout (OR = 0.456, 95%CI: 0.282-0.736) were independently associated with knowledge. Age 26-30 (OR = 1.470, 95%CI: 1.052-2.052), age 31-35 (OR = 1.489, 95%CI: 1.097-2.022), age 36-40 (OR = 0.328, 95%CI: 1.010-1.746), age 41-44 (OR = 1.548, 95%CI: 1.091-2.198), and not having hyperuricemia (OR = 0.512, 95%CI: 0.345-0.760) were independently associated with attitude. White collar/employee (OR = 0.386, 95%CI: 0.285-0.521), educator (OR = 0.534, 95%CI: 0.317-0.899), healthcare worker (OR = 0.341, 95%CI: 0.236-0.493), having siblings (OR = 0.725, 95%CI: 0.573-0.917), and not suffering from hyperuricemia (OR = 0.442, 95%CI: 0.296-0.659), were independently associated with practice. CONCLUSION: Chinese young adults display moderate KAP toward sugar-sweetened beverages. Notably, an association was observed between hyperuricemia and each KAP dimension.

Microflora structure and functional capacity in Tibetan kefir grains and selenium-enriched Tibetan kefir grains: A metagenomic analysis.

Tibetan kefir grains (TKGs) are a complex protein-lipid-polysaccharide matrix composed of various microorganisms. Microorganisms have the benefit of being effective, secure, and controllable when used for selenium enrichment. In this study, selenium-enriched Tibetan kefir grains (Se-TKGs) were made, and the microbiology composition was analyzed through a metagenomic analysis, to explore the influence of selenium enrichment. The microbial composition of TKGs and Se-TKGs, as well as the probiotic species, quorum sensing system (QS) and functional genes were compared and evaluated. Lactobacillus kefiranofaciens was the most abundant microbial species in both communities. Compared with TKGs, Se-TKGs had a much higher relative abundance of acetic acid bacteria. Lactobacillus helveticus was the most common probiotic species both in TKGs and Se-TKGs. Probiotics with antibacterial and anti-inflammatory properties were more abundant in Se-TKGs. QS analysis revealed that Se-TKGs contained more QS system-associated genes than TKGs. Moreover, Kyoto Encyclopedia of Genes and Genomes analysis revealed that the pathway for human disease ko01501 had the greatest relative abundance in both TKGs and Se-TKGs. Compared with TKGs, Se-TKGs demonstrated a greater relative abundance of different drug resistance-related metabolic pathways. Additionally, linear discriminant analysis effect size was used to examine the biomarkers responsible for the difference between the two groups. In this study, we focused on the microbiological structure of TKGs and Se-TKGs, with the aim of establishing a foundation for a more thorough investigation of Se-TKGs and providing a basis for exploring potential future use.

Characteristics and Outcomes of Anti-interferon Gamma Antibody-Associated Adult Onset Immunodeficiency.

PURPOSE: Anti-interferon gamma antibody (AIGA) is a rare cause of adult onset immunodeficiency, leading to severe disseminated opportunistic infections with varying outcomes. We aimed to summarize the disease characteristics and to explore factors associated with disease outcome. METHODS: A systematic literature review of AIGA associated disease was conducted. Serum-positive cases with detailed clinical presentations, treatment protocols, and outcomes were included. The patients were categorized into controlled and uncontrolled groups based on their documented clinical outcome. Factors associated with disease outcome were analyzed with logistic regression models. RESULTS: A total of 195 AIGA patients were retrospectively analyzed, with 119(61.0%) having controlled disease and 76 (39.0%) having uncontrolled disease. The median time to diagnosis and disease course were 12 months and 28 months, respectively. A total of 358 pathogens have been reported with nontubercular mycobacterium (NTM) and Talaromyces marneffei as the most common pathogens. The recurrence rate was as high as 56.0%. The effective rates of antibiotics alone, antibiotics with rituximab, and antibiotics with cyclophosphamide were 40.5%, 73.5%, and 75%, respectively. In the multivariate logistic analysis, skin involvement, NTM infection, and recurrent infections remained significantly associated with disease control, with ORs of 3.25 (95% CI 1.187 ~ 8.909, P value = 0.022), 4.74 (95% CI 1.300 ~ 17.30, P value = 0.018), and 0.22 (95% CI 0.086 ~ 0.551, P value = 0.001), respectively. The patients with disease control had significant AIGA titer reduction. CONCLUSIONS: AIGA could cause severe opportunistic infections with unsatisfactory control, particularly in patients with recurrent infections. Efforts should be made to closely monitor the disease and regulate the immune system.

Micro-inflammation related gene signatures are associated with clinical features and immune status of fibromyalgia.

BACKGROUND: Fibromyalgia (FM) is a multifaceted disease. Along with the genetic, environmental and neuro-hormonal factors, inflammation has been assumed to have role in the pathogenesis of FM. The aim of the present study was to explore the differences in clinical features and pathophysiology of FM patients under different inflammatory status. METHODS: The peripheral blood gene expression profile of FM patients in the Gene Expression Omnibus database was downloaded. Differentially expressed inflammatory genes were identified, and two molecular subtypes were constructed according to these genes used unsupervised clustering analysis. The clinical characteristics, immune features and pathways activities were compared further between the two subtypes. Then machine learning was used to perform the feature selection and construct a classification model. RESULTS: The patients with FM were divided into micro-inflammation and non-inflammation subtypes according to 54 differentially expressed inflammatory genes. The micro-inflammation group was characterized by more major depression (p = 0.049), higher BMI (p = 0.021), more active dendritic cells (p = 0.010) and neutrophils. Functional enrichment analysis showed that innate immune response and antibacterial response were significantly enriched in micro-inflammation subtype (p < 0.050). Then 5 hub genes (MMP8, ENPP3, MAP2K3, HGF, YES1) were screened thought three feature selection algorithms, an accurate classifier based on the 5 hub DEIGs and 2 clinical parameters were constructed using support vector machine model. Model scoring indicators such as AUC (0.945), accuracy (0.936), F1 score (0.941), Brier score (0.079) and Hosmer-Lemeshow goodness-of-fit test (χ2 = 4.274, p = 0.832) proved that this SVM-based classifier was highly reliable. CONCLUSION: Micro-inflammation status in FM was significantly associated with the occurrence of depression and activated innate immune response. Our study calls attention to the pathogenesis of different subtypes of FM.

Hyperuricemia and gout increased the risk of long-term mortality in patients with heart failure: insights from the National Health and Nutrition Examination Survey.

BACKGROUND: The prevalence of hyperuricemia, gout, and heart failure (HF) is on the rise, and these conditions often share similar risk factors. The present study aimed to evaluate the relationship among hyperuricemia, gout, HF, and all-cause mortality. METHODS: The data on nonpregnant participants aged ≥ 20 years with or without hyperuricemia, gout, and HF from the National Health and Nutrition Examination Survey 2001-2018 and 2007-2018 were included in this study. The binary logistic regression, Kaplan-Meier curve, Cox proportional-hazards model, and restricted cubic spline analysis were employed to evaluate the relationship among hyperuricemia, gout, HF, and all-cause mortality. RESULTS: Of 204,179,060 and 223,702,171 weighted eligible participants, 40,044,228 (19.6%) and 9,158,600 (4.1%) had hyperuricemia and gout, respectively. Older age, diabetes, stroke, and coronary artery disease were the risk factors for HF among patients with hyperuricemia and gout. The median survival time was 7.00 years and 6.25 years and the 5-year survival rate was 59.9% and 55.9% for patients with HF and hyperuricemia and those with HF and gout, respectively. Patients with hyperuricemia or gout were 2.46 and 2.35 times more likely to have HF and 1.37 and 1.45 times more likely to experience all-cause mortality compared with those who did not exhibit these conditions. The restricted cubic spline showed a nonlinear correlation between uric acid levels and HF and a J-shaped correlation between uric acid levels and all-cause mortality. CONCLUSIONS: Ambulatory patients with hyperuricemia or gout were more likely to have HF compared with those without hyperuricemia or gout. Patients with HF with hyperuricemia or gout were more likely to experience all-cause mortality in the long-term follow-up.

Aspergillus cristatus attenuates DSS-induced intestinal barrier damage through reducing the oxidative stress, regulating short-chain fatty acid and inhibiting MAPK signaling pathways.

BACKGROUND: Probiotics are regarded as a promising strategy for relieving colitis caused by dextran sulfate sodium (DSS). One of the dominant probiotic fungi in Fuzhuan brick tea is identified as Aspergillus cristatus, but whether it can effectively improve colitis remains poorly understood. Here, the improving effect of A. cristatus on colitis was investigated. RESULTS: Our results showed that A. cristatus intervention prominently alleviated gut damage as evidenced by the inhibition of shortened colon length, goblet cell depletion, and histological injury. Mechanistically, after administration with low concentrations of A. cristatus H-1 and A. cristatus S-6, the expression of interleukin-6, tumor necrosis factor-α, interleukin-1ß, nitric oxide, and malondialdehyde were significantly downregulated, and the content of glutathione, catalase, interleukin-10, immunoglobulin G, claudin-1, occludin, and zonula occludens-1 were effectively upregulated. More importantly, live A. cristatus supplementation lightened DSS-induced gut barrier damage by suppressing activation of the mitogen-activated protein kinase (MAPK) signaling pathway, increasing the synthesis of short-chain fatty acids (SCFAs) and stimulating the increase in peroxisome proliferator-activated receptor γ expression. CONCLUSION: Together, A. cristatus can attenuate DSS-induced intestinal barrier damage through reducing the oxidative stress, regulating SCFA and inhibiting MAPK signaling pathways (P38/JNK/ERK). Our findings indicate that A. cristatus replenishment has potential as a new probiotic fungi to reduce DSS-induced colitis. © 2022 Society of Chemical Industry.

Recurrent spontaneous pneumoperitoneum secondary to intestinal dilatation caused by allied disorders of Hirschsprung's disease: a case report.

BACKGROUND: Allied disorders of Hirschsprung's disease (ADHD) mainly present with bowel obstruction, intestinal dilatation, and chronic constipation, while recurrent spontaneous pneumoperitoneum was rarely reported. We aimed to report a case of recurrent spontaneous pneumoperitoneum caused by ADHD. CASE PRESENTATION: A 59-year-old female patient presented with progressive and severe constipation in the past 30 years. She suffered from abdominal discomfort, which was described as 'gurgling' during the last three years. Radiography showed free-air and intestinal dilatation, without any other diseases, and she was identified with recurrent spontaneous pneumoperitoneum. Gastrointestinal transit test indicated gastrointestinal motility disorder, and anorectal manometry confirmed the presence of rectal anus-suppressing reflex. Subtotal colectomy was performed to relieve apparent constipation, and the postoperative pathological examination of the colon demonstrated proliferation of nerve fibers and hyperplasia of myenteric plexuses, as well as a relatively scarcity of ganglion cells in the myenteric plexus. Based on the presentations and the postoperative pathology, she was diagnosed with ADHD. The recurrent spontaneous pneumoperitoneum was regarded as the gas escape from dilated intestines, which was in high pressure. All the symptoms and her mental state were improved after the treatment with gastrointestinal decompression and enteral nutrition. However, during follow-up visits, she had intestinal infection, and suffered from severe diarrhea and water-electrolyte imbalance, and the patient eventually died at 17 months after the diagnosis. CONCLUSION: ADHD could be a rare cause of recurrent spontaneous pneumoperitoneum, and are mainly undiagnosed or misdiagnosed. A full-thickness biopsy of the gastrointestinal tract (especially the small intestine and sigmoid colon) and differential diagnosis are recommended for the definitive diagnosis. While the ADHD have shown a poor prognosis, timely and long-term treatment with intestinal decompression and nutritional therapy could help relieve symptoms and provide a better quality of life for such patients.

A Tale of 3 Asian Cities: How is Primary Care Responding to COVID-19 in Hong Kong, Singapore, and Beijing.

Hong Kong, Singapore, and Beijing have some of the highest numbers of international arrivals and densest living spaces globally, yet these cities have reported low numbers of deaths amid the coronavirus disease 2019 (COVID-19) outbreak. Primary care has played different roles in each of the health systems in combatting the pandemic. Both Hong Kong and Singapore have a 2-tiered health system with the majority of primary care provided in the private sector. The primary care system in Beijing consists of community health facilities, township health centers, and village clinics. The role of primary care in Hong Kong includes using the public primary care clinics as part of an enhanced surveillance program together with accident and emergency departments, as well as triaging patients with suspected infection to hospitals. Singapore's response to COVID-19 has included close cooperation between redeveloped polyclinics and private and public health preparedness clinics to provide screening with swab tests for suspected cases in the primary care setting. Beijing's unique response has consisted of using online platforms for general practitioners to facilitate monitoring among community residents, as well as public health education and a mobilized pharmacy refill program to reduce risk of transmission. Established challenges, however, include shortages of personal protective equipment and the heavy workload for health care staff. Regardless, all 3 cities have demonstrated enhanced preparedness since experiencing the severe acute respiratory syndrome epidemic, and the responses of their primary care systems therefore may offer learning points for other countries during the COVID-19 pandemic.

Uncommon manifestations of a rare disease: a case of autoimmune GFAP astrocytopathy.

BACKGROUND: Manifestations of intractable hyponatremia and hypokalemia in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy have been rarely reported. CASE PRESENTATION: A 75-year-old male patient presented as the case of syndrome of inappropriate antidiuretic hormone secretion (SIADH) and intractable hypokalemia, showed fever, fatigue, and mental disorders. Signs and symptoms of meningoencephalitis, ataxia, and cognitive abnormalities. Magnetic resonance imaging (MRI) revealed multiple white matter lesions of the central nervous system. He had GFAP-IgG in the cerebrospinal fluid (CSF). After treatment with corticosteroids, his symptoms were alleviated gradually, and the level of electrolytes was normal. However, head contrast-enhanced MRI + susceptibility-weighted imaging (SWI) showed a wide afflicted region, and the serum GFAP-IgG turned positive. Considering the relapse of the disease, ha was treated with immunoglobulin and mycophenolate mofetil (MMF) to stabilize his condition. CONCLUSION: This case showed a rare disease with uncommon manifestations, suggesting that careful examination and timely diagnosis are essential for disease management and satisfactory prognosis.

Antimicrobial and anti-biofilm activity of thymoquinone against Shigella flexneri.

Shigella flexneri (Sh. flexneri), a common foodborne pathogen, has become one of the main threats to food safety and human health due to its high pathogenicity and persistent infection. The objective of this study was to explore the antimicrobial and anti-biofilm activities and the possible mechanism of thymoquinone (TQ) against Sh. flexneri. The minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of TQ against Sh. flexneri were 0.4 and 0.5 mg/mL, respectively. TQ showed bactericidal activity against Sh. flexneri in culture medium and milk system. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) observations demonstrated that TQ could induce abnormal cell morphology and destroy cell membrane. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis suggested that TQ could inhibit protein synthesis in Sh. flexneri. Also, at sub-inhibitory concentrations (SICs), TQ exhibited an inhibitory effect on Sh. flexneri biofilm formation, which was confirmed by crystal violet quantitative analysis and SEM observation. Real-time quantitative PCR (RT-qPCR) analyses revealed that TQ downregulated the expression of genes involved in Sh. flexneri biofilm formation. Thus, TQ has potential as a natural antimicrobial and anti-biofilm agent to address the contamination and infection caused by Sh. flexneri. KEY POINTS: • Antimicrobial and anti-biofilm activity of TQ on Shigella flexneri were investigated. • TQ inhibited biofilm formation by Shigella flexneri. • TQ provided a new strategy for Shigella flexneri control.

General practitioner trainees' career perspectives after COVID-19: a qualitative study in China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has been a worldwide public health emergency that has put great pressure on medical workers and the medical system. General Practitioners (GPs) played an important role in controlling the epidemic, and GP trainees also took an active part in this approach. This study was to explore Chinese GP trainees' career perspectives after COVID-19. METHODS: We conducted a qualitative research study which included 12 GP trainees from three teaching hospitals in China. Semi-structured telephone interviews were conducted. Grounded theory and thematic analysis were used to code the data and identify categories and factors. RESULTS: Eleven participants chose to continue a GP career after COVID-19, and nearly half of the participants strengthened their determination to dedicate themselves to this career. Only one participant decided to change the career choice because of interest in another specialty. Four main themes influencing GP trainees' perceptions of career development after COVID-19 emerged from the interviews: changes of GPs' work content in COVID-19, challenges of being a GP, psychological changes of the career, how to provide better primary care. Although some negative psychological changes existed, most of participants were inspired by role models and medical colleagues. They had more in-depth understanding of GPs' role and responsibility during COVID-19, and exhibited intensions for self-improvement in career development, especially in public health education and self-protection in preventing infectious diseases. In addition, the wide use of telemedicine provided a new work way for GP trainees. However, challenges, such as increased workloads, low income, lack of resources in primary medical institutions, and distrust of GPs are faced by trainees during the outbreak. CONCLUSIONS: Overall, no substantial changes were seen in the career choice of GP trainees after COVID-19 outbreak. However, they were inspired and had an in-depth understanding about the GP's work and responsibility during an epidemic. Owing to the challenges faced by the GPs, measures are needed to improve the GP education and work environment in the training phase.

IgG4-related fibrosing mediastinitis: clinical presentation, treatment efficacy and comparison with IgG4-RD without fibrosing mediastinitis.

OBJECTIVES: This study aimed to investigate the clinical characteristics and treatment efficacy of immunoglobulin G4 (IgG4)-related fibrosing mediastinitis (IgG4-RFM) and to compare IgG4-RFM patients with IgG4-related disease (IgG4-RD) patients without fibrosing mediastinitis (FM). METHODS: Twenty IgG4-RFM patients and 60 randomly matched IgG4-RD patients without FM from a prospective cohort at the Peking Union Medical College Hospital (PUMCH) were enrolled from 2011 to 2019. Patient demographic data, clinical characteristics, laboratory parameters and treatment efficacy were analysed. RESULTS: The prevalence of IgG4-RFM in our cohort was 2.8%. The average age was 51.7±14.8 years, and the patients were predominantly male (60.0%). Periaortic masses (75.0%) and paravertebral masses (35.0%) were the most common characteristic imaging findings of IgG4-RFM. Compared with male patients with IgG4-RFM, a lower percentage of female patients had abdominal aorta involvement (p=0.015). IgG4-RFM patients had a shorter disease duration; lower percentage of allergy history, submandibular gland involvement, and pancreas involvement; lower serum IgG4; higher erythrocyte sedimentation rate (ESR) and high-sensitivity C-reactive protein (hsCRP) levels; and a higher percentage of single organ involvement than patients without FM (p<0.001, p=0.008, p=0.033, p=0.001, p=0.027, p=0.007, p=0.004 and p=0.047, respectively). After treatment, 94.7% of patients achieved a mediastinal soft tissue reduction of >30%. CONCLUSIONS: IgG4-RFM is a distinct fibrotic subtype of IgG4-RD. Periaortic masses and paravertebral masses were the most common characteristic imaging findings of IgG4-RFM. Most IgG4-RFM patients respond well to glucocorticoid (GC) and immunosuppressant treatments.

Sex disparities in clinical characteristics and prognosis of immunoglobulin G4-related disease: a prospective study of 403 patients.

OBJECTIVES: To study the impact of sex on the clinical presentation of IgG4-related disease (IgG4-RD). METHODS: We prospectively enrolled 403 newly diagnosed IgG4-RD patients. We compared the demographic features, clinical manifestations, organ involvement, laboratory tests and treatment outcomes between female and male patients. The organs involved were divided into superficial organs (salivary glands, lacrimal glands, orbit, sinus and skin) and internal organs (all the other organs). The patients treated with glucocorticoids with or without additional immunosuppressants were included in the assessment of treatment outcomes, and potential confounding factors were corrected by propensity score matching or multivariate Cox regression analysis. RESULTS: Female patients showed younger age at both symptom onset and diagnosis, and a longer interval between symptom onset and diagnosis. Allergy history, Mikulicz's disease and thyroiditis were more common in female patients, while autoimmune pancreatitis, sclerosing cholangitis and retroperitoneal fibrosis were more common in male patients. In accordance, female patients more frequently presented with superficial organ involvement, while male patients more frequently had internal organ involvement, and the discrepancy was more prominent in the patients with older age. Male sex was associated with higher peripheral eosinophils, CRP and IgG4 levels at baseline. In response to glucocorticoid-based therapies, male sex was associated with a higher IgG4-RD responder index during follow-up as well as a greater risk of relapse (hazard ratio 3.14, P = 0.003). CONCLUSION: Our study revealed the sex disparities in clinical characteristics of IgG4-RD, and indicated that male sex was independently associated with worse prognosis in response to glucocorticoid-based therapies.

Fatal myositis and spontaneous haematoma induced by combined immune checkpoint inhibitor treatment in a patient with pancreatic adenocarcinoma.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have achieved unprecedented success in cancer treatment over the past decade. The application of ICIs hasled to the discovery of various types of immune-related adverse events (irAEs). Here, we report a case of fatal myositis and spontaneous haematoma following concurrent treatment of nivolumab and ipilimumab for pancreatic adenocarcinoma. CASE PRESENTATION: A 71-year-old gentleman with pancreatic adenocarcinoma underwent the Whipple procedure in September 2014. The patient received 8 cycles of adjuvant chemotherapy with gemcitabineand achieved a complete responsein April 2015. Treatment with the PD-1 inhibitor nivolumab was started due to suspected tumour recurrence in November 2015. In August 2016, the CTLA-4 inhibitor ipilimumab was added to nivolumab for 2 cycles. Eight weeks after the last dose, the patient developed severe myositis complicated with spontaneous haematomain skeletalmuscle. Pathology of the skeletal muscle autopsy revealed lymphocytic infiltration. Intense immunosuppressive therapy, including high-dose corticosteroids and methotrexate, resulted in clinical success in the treatment of myositis. However, the patient died of cancer recurrence. CONCLUSION: Myositis due to immunotherapy can be a fatal adverse event of ICIs, which requires close monitoring and cautious management.

Blood utilization in five Chinese hospitals shows low hemoglobin thresholds in medical patients.

BACKGROUND: The number of red blood cell units transfused per capita in China is lower than in western countries and the reason(s) for the difference is unknown. STUDY DESIGN AND METHODS: We randomly chose 5050 transfused patients from five Chinese hospitals. We compared transfused cases to nontransfused controls matched for the same underlying diagnosis. We assessed the pretransfusion hemoglobin (Hb) trigger and other clinical characteristics associated with transfusion. After stratifying by underlying disease, we compared pretransfusion Hb level in Chinese hospitals to 12 US hospitals. RESULTS: In 5050 patients who received transfusion, the pretransfusion Hb levels were lower in medical (6.3 g/dL) compared to surgical patients receiving transfusion postoperatively (8.1 g/dL). In patients with nonsurgical diagnoses, the pretransfusion Hb was much lower than that in the United States; the difference in mean Hb level varied by underlying diagnosis from 0.4 to 1.8 g/dL. In case-control analysis of cases (n = 1356) compared to controls (n = 1201), the pretransfusion Hb showed the strongest association with transfusion. Compared to 10 g/dL, the odds ratio (95% confidence interval) for pretransfusion Hb of 7 to 7.9 g/dL was 37.7 (24.8-57.4). CONCLUSION: Transfusion triggers in five Chinese hospitals appear comparable to those in the United States for surgical patients; however, medical patients have lower pretransfusion Hb levels (approx. 6 g/dL). Of the factors assessed, the pretransfusion Hb was most strongly associated with transfusion. The clinical impact of lower transfusion thresholds used in China is unknown.

Survey results of job status of residents in a standardized residency training program.

BACKGROUND: The history of standardized residency training programs (SRTP) in China is not long. As one of the top medical colleges in China, Peking Union Medical College Hospital (PUMCH) has the history and experience of the oldest SRTP in the country. Understanding the job status of PUMCH residents would be conducive to a better development of the national resident training in the future. METHODS: This study analyzed the demographic information, job burnout scale, working time, and job status of postgraduate year 1-3 residents that took part in the SRTP of the Department of Internal Medicine of PUMCH in August 2017. RESULTS: The survey data of 159 residents (including PUMCH residents, local-resident-trainees, and clinical postgraduates) were collected. The average working time was 11.38 ± 1.55 h per day and 83.28 ± 8.80 h per week. The average night shift frequency was 4.74 ± 0.59 days. There were 100 residents (62.2%) with symptoms of job burnout, which had a certain correlation with working time (p < 0.05). The self-evaluation of the clinical postgraduates about their working quality of life was lower than that of other residents (p < 0.05). There were various reasons for long working-time, great work pressure, and job burnout. Job burnout was independently associated with the average working time per day (OR = 2.35, 95% CI: 1.47-3.75, P < 0.001) and average length of duty period (OR = 1.52, 95% CI: 1.26-1.84, P < 0.001). CONCLUSION: The job burnout of residents that took part in SRTP at the PUMCH could not be ignored, which had a certain correlation with work time and early training background.

Wilson's disease combined with systemic lupus erythematosus: a case report and literature review.

BACKGROUND: Wilson's disease (WD) is an inherited disorder in which defective biliary excretion of copper leads to its accumulation, particularly in the liver and brain. Systemic lupus erythematosus (SLE) is a multi-system disorder that can manifest in any system. Cases with concomitant WD and SLE, unrelated to treatment with penicillamine, have been rarely reported. CASE PRESENTATION: We report a case of a young woman who had typical neuropsychiatric symptoms and laboratory tests results of WD. She also had concomitant massive hematuria and proteinuria, fever, multiple positive autoimmune antibodies, hypocomplementemia, abnormal lumbar puncture findings and evidence of Sjögren syndrome, which are all rare in WD. Hence, we considered the diagnosis of SLE. Tapering of steroid dosage also confirmed the diagnosis. CONCLUSION: Wilson's disease and SLE have varied clinical manifestations. Herein, we reported a rare case in which the two conditions concomitantly existed. In clinical practice, differential diagnosis of the two diseases is necessary for patients with hepatic, neurological, and psychiatric manifestations.

Simultaneous determination of tilianin and its metabolites in mice using ultra-high-performance liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study.

Tilianin is an active flavonoid glycoside found in many medical plants. Data are lacking regarding its pharmacokinetics and disposition in vivo. The objective of this study was to develop a sensitive, reliable and validated ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method to simultaneously quantify tilianin and its main metabolites and to determine its pharmacokinetics in wild-type and breast cancer resistance protein knockout (Bcrp1-/-) FVB mice. Chromatographic separation was accomplished on a C18 column by utilizing acetonitrile and 0.5 mm ammonium acetate as the mobile phase. Mass spectrometric detection was performed using electrospray ionization in both positive and negative modes. The results showed that the precision, accuracy and recovery, as well as the stability of tilianin and its metabolites in mouse plasma, were all within acceptable limits. Acacetin-7-glucuronide and acacetin-7-sulfate were the major metabolites of tilianin in mouse plasma. Moreover, systemic exposure of acacetin-7-sulfate was significantly higher in Bcrp1 (-/-) FVB mice compared with wild-type FVB mice. In conclusion, the fully validated UHPLC-MS/MS method was sensitive, reliable, and was successfully applied to assess the pharmacokinetics of tilianin in wild-type and Bcrp1 (-/-) FVB mice. Breast cancer resistance protein had a significant impact on the elimination of the sulfated metabolite of tilianin in vivo.