Exploring the Localization of Siderophore-Mediated Cargo Delivery in Gram-Negative Bacteria Using 3-Hydroxypyridin-4(1H)-one-Fluorescein Probes.

The design of siderophore-antibiotic conjugates is a promising strategy to overcome drug resistance in negative bacteria. However, accumulating studies have shown that only those antibiotics acting on the cell wall or cell membrane multiply their antibacterial effects when coupled with siderophores, while antibiotics acting on targets in the cytoplasm of bacteria do not show an obvious enhancement of their antibacterial effects when coupled with siderophores. To explore the causes of this phenomenon, we synthesized several conjugate probes using 3-hydroxypyridin-4(1H)-ones as siderophores and replacing the antibiotic cargo with 5-carboxyfluorescein (5-FAM) or malachite green (MG) cargo. By monitoring changes in the fluorescence intensity of FAM conjugate 20 in bacteria, the translocation of the conjugate across the outer membranes of Gram-negative pathogens was confirmed. Further, the use of the fluorogen activating protein(FAP)/MG system revealed that 3-hydroxypyridin-4(1H)-one-MG conjugate 26 was ultimately distributed mainly in the periplasm rather than being translocated into the cytosol of Escherichia coli and Pseudomonas aeruginosa PAO1. Additional mechanistic studies suggested that the uptake of the conjugate involved the siderophore-dependent iron transport pathway and the 3-hydroxypyridin-4(1H)-ones siderophore receptor-dependent mechanism. Meanwhile, we demonstrated that the conjugation of 3-hydroxypyridin-4(1H)-ones to the fluorescein 5-FAM can reduce the possibility of the conjugates crossing the membrane layers of mammalian Vero cells by passive diffusion, and the advantages of the mono-3-hydroxypyridin-4(1H)-ones as a delivery vehicle in the design of conjugates compared to the tri-3-hydroxypyridin-4(1H)-ones. Overall, this work reveals the localization rules of 3-hydroxypyridin-4(1H)-ones as siderophores to deliver the cargo into Gram-negative bacteria. It provides a theoretical basis for the subsequent design of siderophore-antibiotic conjugates, especially based on 3-hydroxypyridin-4(1H)-ones as siderophores.

Improving crop health by synthetic microbial communities: Progress and prospects.

Crop health directly affects yields and food security. At present, agrochemicals such as fertilizers and pesticides are mainly used in agricultural production to promote crop health. However, long-term excessive utilization of agrochemicals will damage the ecological environment of farmlands and increase the safety risk of agricultural products. It is urgent to explore efficient and environment-friendly agricultural products. Rhizosphere microbiome are considered as the second genome of plants, which are closely related to crop health. Understanding the key functional microbes, microbe-microbe interactions, and plant-microbe interactions are fundamental for exploring the potential of beneficial microbes in promoting crop health. However, due to the heterogeneity and complexity of the natural environment, stimulating the function of indigenous microorganisms remains uncertain. Synthetic microbial community (SynCom) is an artificial combination of two or more different strain isolates of microorganisms, with different taxonomic, genetic, or functional characteristic. Because of the advantages of maintaining species diversity and community stability, SynCom has been widely applied in the fields of human health, environmental governance and industrial production, and may also have great potential in promoting crop health. We summarized the concept and research status of SynCom, expounded the principles and methods of constructing SynCom, and analyzed the research on the promotion of crop health by exploring the mechanism of plant-microbe interactions, promoting plant growth and development, and improving stress resistance. Finally, we envisaged the future prospects to guide the using SynCom to improve crop health.

SCN4A-related congenital myopathy in a Han Chinese patient: A case report and literature review.

SCN4A mutations have been shown to be associated with myotonia, paramyotonia congenita, and periodic paralyses. More recently, loss-of-function variants in the SCN4A gene were also noted to be associated with rarer, autosomal recessive forms of congenital myasthenic syndrome and congenital myopathy. Diagnosis is challenging as the initial clinical presentation and histological features on muscle biopsies are non-specific. We report a Han Chinese patient presented with congenital myopathy with two missense SCN4A variants. The patient had an antenatal history of reduced fetal movements, polyhydramnios and a very preterm birth. At birth, she was noted to have low Apgar score, respiratory distress syndrome and hypotonia. Delayed motor development was noted in early childhood. Dysmorphic features such as an elongated face, dolichocephaly and high arched palate were present. At 16 years of age, the patient developed progressive muscle weakness and was wheelchair-bound by age 20. Muscle biopsy revealed non-specific changes only. Targeted hereditary myopathy panel testing by next generation sequencing revealed two previously unreported missense variants c.1841A > T p.(Asn614Ile) and c.4420G > A p.(Ala1474Thr) in the SCN4A gene. The clinical features of SCN4A-related congenital myopathy and myasthenic syndrome were reviewed. This case exemplifies the utility of next generation sequencing in the diagnosis of undifferentiated muscle disease.

Identification and interruption of inheritance of familial cryptic translocations: A case report.

BACKGROUND: Cryptic translocations can be identified via genetic analysis of aborted tissues or malformed infants, but it is difficult to deduce the parental origins of the translocations. In the absence of such information, it is not easy to distinguish translocations from normal embryos during pre-implantation genetic testing, that seeks to block familial transmission of translocations. METHODS: Here, we present a new method that detects cryptic translocations and blocks familial transmission thereof. Whole-genome, low-coverage mate-pair sequencing (WGLMPS) revealed chromosome breakpoint sequences, and preimplantation genetic haplotyping (PGH) was then used to discard embryos with cryptic translocations. RESULTS: Cryptic translocations were found in all four families, and familial transmission was successfully blocked in one family. CONCLUSION: Whole-genome, low-coverage mate-pair sequencing combined with preimplantation genetic haplotyping methods powerfully and practically identify cryptic translocations and block familial transmissions.

Associations between social loneliness trajectories and chronotype among adolescents.

Late chronotype during adolescence is a critical risk factor for poor physical and mental health among adolescents. While social loneliness is confirmed to negatively influence sleep behaviors, the long-term effect of social loneliness on chronotype remains unknown. This study aims to investigate whether social loneliness trajectories from middle childhood to adolescence are associated with chronotype in late adolescence and examine the potential sex differences in these associations. Data were obtained from 2398 adolescents who participated in the Child and Adolescent Behaviors in Long-Term Evolution project. Chronotype was calculated as the midpoint of sleep on free days adjusted for sleep debt. Group-based trajectory modeling and multiple linear regression were employed to establish social loneliness trajectories and determine their associations with chronotype. Social loneliness trajectories were significantly associated with chronotype and varied by sex. Specifically, boys following a high-decreasing trajectory had earlier chronotype during late adolescence than did those following a low-decreasing trajectory (B = - 0.07; p < 0.05). By contrast, girls following a low-to-moderate-increasing trajectory exhibited later chronotype than did those following a low-stable trajectory (B = 0.07; p < 0.01). Social loneliness trajectories, especially those displaying significant fluctuations over time, are critical indicators influencing chronotype among adolescents. Furthermore, these trajectories and their associations with chronotype display sex differences. These findings highlight the need for early interventions for psychological factors such as social loneliness to ensure that the late chronotype can be prevented. In addition, sex variations must be considered.

Associations between social jetlag trajectories and body mass index among young adults.

STUDY OBJECTIVES: This study employed longitudinal data collected repeatedly from individuals over the course of several years to examine the trajectories of social jetlag from ages 11 to 22 years and their associations with subsequent body mass index (BMI). Potential sex differences were also investigated. METHODS: Data were obtained from two longitudinal studies conducted in Taiwan (N = 4287). Social jetlag was defined as ≥ 2 hours of absolute difference in sleep midpoint between weekdays and weekends. BMI was calculated using weight (kg)/height(m)2 and categorized as underweight (<18 kg/m2), normal weight (18 kg/m2 ≤ BMI < 24 kg/m2), overweight (24 kg/m2 ≤ BMI < 27 kg/m2), and obese (≥27 kg/m2). Group-based trajectory modeling and multinomial logistic regression were applied to investigate study objectives. RESULTS: Four distinct trajectories of social jetlag throughout the adolescent years were identified, with corresponding proportions as follows: low-stable (42%), moderate-decreasing (19%), low-increasing (22%), and chronic (17%) trajectories. Among males, the risk of being underweight (aOR, 1.96; 95% CI: 1.35 to 2.84) or obese (aOR, 1.40; 95% CI: 1.02 to 1.92) was higher in individuals with a low-increasing trajectory than in those with a low-stable trajectory. Among females, those with a low-increasing (aOR, 1.61; 95% CI: 1.02 to 2.54) or chronic (aOR, 2.04; 95% CI: 1.27 to 3.25) trajectory were at a higher risk of being obese relative to those with a low-stable trajectory. CONCLUSIONS: Addressing the development of increasing or chronic social jetlag during adolescence can help prevent abnormal BMI in young adulthood. Practitioners should consider sex differences in treatment or consultation.

The effect of childhood depression trajectories on sugar-sweetened beverage habit trajectories in adolescence: Exploring sleep problems as a mediator.

Although depression has been linked to the habit of consuming sugar-sweetened beverages (SSBs), little is known about their long-term relationships and the mediating role of sleep problems. This study examines the associations between childhood depressive symptoms trajectories and adolescent SSB-habit trajectories and whether these associations were mediated by sleep problems. Data came from 1560 adolescents participating in a longitudinal study across grades 1 through 12 in northern Taiwan. Group-based trajectory modeling was used to identify development of childhood depressive symptoms and an SSB habit in adolescence. Multinomial logistic regression was conducted to examine the influence of childhood depressive symptoms and adolescent SSB habit. Mediation analysis was conducted to test whether sleep problems mediated the associations examined. Four distinct trajectories of childhood depressive symptoms were identified: low-stable (30.79%), moderate-stable (42.32%), increasing (12.29%), and high-stable (11.60%). Three distinct trajectories of SSB habit in adolescence were identified: low-stable (44.32%), increasing (15.02%), and high-stable (40.65%). Children who had moderate-stable (aOR = 1.35; CI: 1.04-1.77), high-stable (aOR = 2.01; CI: 1.28-3.15), or increasing (aOR = 1.97; CI: 1.26-3.06) trajectories of depressive symptoms relative to those in the low-stable group were significantly more likely to belong to the high-stable trajectory of SSBs than to the low-stable SSBs group. The Z-mediation test showed that sleep problems significantly mediated the associations between trajectories of childhood depressive symptoms and trajectories of SSBs during adolescence (all p < 0.05). Childhood depressive symptoms conferred risks for adolescent SSB habits; and the effects were seen, in part, through increasing sleep problems.

Associations of timing, level, and pattern of secondhand smoke exposure with early alcohol initiation: A cohort study.

BACKGROUND: Few studies explored the longitudinal link between early-life secondhand smoke (SHS) exposure and later alcohol initiation despite its risk for child behavioral difficulties. We examined the associations of the timing, level, and pattern of SHS exposure from pregnancy to childhood with early alcohol initiation and evaluated the sex differences in these associations. METHODS: Data were from 16,440 participants of the Taiwan Birth Cohort Study conducted when the children were aged 6 months, 18 months, 3 years, 5.5 years, 8 years, and 12 years. Group-based trajectory modeling was applied to identified patterns of SHS exposure. A series of multiple logistic regression were conducted to examine study hypotheses. RESULTS: Exposure to prenatal SHS was associated with an increased risk of early alcohol initiation (adjusted odds ratio [aOR] = 1.17, 95% confidence interval [CI] = 1.06, 1.30). Compared with the adolescents with a persistent-low-exposure trajectory, those who exhibited prenatal-high-decreasing (aOR = 1.18, 95% CI = 1.04, 1.35) or persistent-high-exposure (aOR = 1.27, 95% CI = 1.12, 1.45) patterns exhibited increased risks of early alcohol initiation. Those with higher cumulative levels of SHS exposure also exhibited an increased risk of early alcohol initiation (aOR = 1.03, 95% CI = 1.01, 1.04). Sex differences were also observed. CONCLUSIONS: Varying timing, levels, and longitudinal patterns of SHS exposure during early life had differential effects on early alcohol initiation, with the effects differing by sex. Targeting SHS exposure while considering the nature of exposure and sex differences could help prevent and curb alcohol use in adolescents.

Effect of noninvasive embryo viability testing versus conventional IVF on the live birth rate in IVF/ICSI patients: a study protocol for a double-blind, multicenter, randomized controlled trial.

BACKGROUND: Preimplantation genetic testing for aneuploidy (PGT-A) was demonstrated to be superior to conventional IVF in reducing the incidence of miscarriage and abnormal offspring after the first embryo transfer (ET). PGT-A requires several embryo trophectoderm cells, but its negative impacts on embryo development and long-term influence on the health conditions of conceived children have always been a concern. As an alternative, noninvasive PGT-A (niPGT-A) approaches using spent blastocyst culture medium (SBCM) achieved comparable accuracy with PGT-A in several pilot studies. The main objective of this study is to determine whether noninvasive embryo viability testing (niEVT) results in better clinical outcomes than conventional IVF after the first embryo transfer. Furthermore, we further investigated whether niEVT results in higher the live birth rate between women with advanced maternal age (AMA, > 35 years old) and young women or among patients for whom different fertilization protocols are adopted. METHODS: This study will be a double-blind, multicenter, randomized controlled trial (RCT) studying patients of different ages (20-43 years) undergoing different fertilization protocols (in vitro fertilization [IVF] or intracytoplasmic sperm injection [ICSI]). We will enroll 1140 patients at eight reproductive medical centers over 24 months. Eligible patients should have at least two good-quality blastocysts (better than grade 4 CB). The primary outcome will be the live birth rate of the first embryo transfer (ET). Secondary outcomes will include the clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, cumulative live birth rate, ectopic pregnancy rate, and time to pregnancy. DISCUSSION: In this study, patients who undergo noninvasive embryo viability testing (niEVT) will be compared to women treated by conventional IVF. We will determine the effects on the pregnancy rate, miscarriage rate, and live birth rate and adverse events. We will also investigate whether there is any difference in clinical outcomes among patients with different ages and fertilization protocols (IVF/ICSI). This trial will provide clinical evidence of the effect of noninvasive embryo viability testing on the clinical outcomes of the first embryo transfer. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) Identifier: ChiCTR2100051408. 9 September 2021.

Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is Associated with Disease Activity and Risk of Incident Cardiovascular Disease in Patients with Systemic Lupus Erythematosus.

To study the relationship of serum PCSK9 and disease activity and major adverse cardiovascular events (MACEs) in systemic lupus erythematosus (SLE). Consecutive patients who fulfilled ≥ 4 ACR criteria for SLE and consented for a biomarker study in 2009-2013 were included. Stored serum samples were assayed for PCSK9. PCSK9 levels were correlated with SLE disease activity scores. Patients were divided into two groups according to the median PCSK9 level and new MACEs over time were evaluated. The effect of PCSK9 level on MACEs and mortality was studied by Cox regression, adjusted for confounders. A total of 539 SLE patients were studied (93% women, age 41.9 ± 14.0 years). The median PCSK9 level at baseline was 220 ng/ml. Patients with higher PCSK9 (≥ 220 ng/ml; n = 269) had significantly higher SLE disease activity index (SLEDAI) than those with lower PCSK9 (< 220 ng/ml; n = 270). PCSK9 levels were significantly higher in patients with active renal than active non-renal SLE, which in turn were significantly higher than those with inactive SLE or healthy controls. PCSK9 level correlated with SLEDAI in the overall population (ρ = 0.30; p < 0.001). Over 91.3 ± 18.6 months, 29 patients developed 31 MACEs and 40 patients succumbed (25% for vascular events). The cumulative incidence of MACEs at 5 years was 4.8% in the higher PCSK9 and 1.1% in the lower PCSK9 group (HR2.51[1.11-5.70]; p = 0.03). Cox regression revealed higher PCSK9 was significantly associated with MACEs (HR1.003[1.000-1.005] per ng/ml; p = 0.02) independent of age, sex, renal function, baseline disease activity score, traditional atherosclerotic risk factors, antiphospholipid antibody and the use of aspirin/warfarin, statins and immunosuppressive drugs. PCSK9 level was also independently associated with all-cause (HR1.002[1.000-1.004] per ng/ml; p = 0.03) and vascular mortality (HR1.004[1.000-1.007]; p = 0.04). We concluded that serum PCSK9 level correlates with SLE disease activity. Higher serum PCSK9 levels are associated with increased risk of cardiovascular events and mortality in SLE.

In vitro tests to evaluate embryotoxicity and irritation of Chinese herbal medicine (Pentaherbs formulation) for atopic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD) is a common chronic inflammatory skin disorder and its prevalence is increasing in the last few decades. No treatment can cure the condition. Pregnancy often worsens the clinical manifestation. There are considerable interests in Chinese Herbal Medicine (CHM) as an alternative treatment for AD. A well tolerated CHM formula (Pentaherbs formulation, PHF) has been proven efficacious in improving life quality and reducing topical corticosteroid use in children with moderate-to-severe AD. However, safety data of PHF are not available. AIM OF THE STUDY: Our study aimed to evaluate the safety of PHF and its 5 individual herbal extracts, including embryotoxicity by Embryonic Stem Cell Test (EST) and irritation by Skin Irritation Test (SIT). MATERIALS AND METHODS: Quality of 5 herbal extracts of PHF was confirmed by chromatography. In EST, mouse embryonic stem cell line (D3) and mouse fibroblast cell line (3T3) were used to study potential embryotoxicity. Three endpoints were assessed by concentration-response curves after 10 days' culture: 50% inhibition of D3 differentiation into beating cardiomyocytes (ID50D3), 50% cytotoxic effects on D3 (IC50D3) and on fibroblasts (IC503T3). A biostatistically based prediction model (PM) was applied to predict the embryotoxic potentials of each CHM. In SIT, epidermis equivalent commercially available kits (EpiDerm™) were used, and concentration-viability curves were obtained by MTT assay to detect skin irritations of each CHM. RESULTS: Chemical authentication confirmed that 5 test herbal extracts contained their main active compounds. EST results indicated that the formula PHF and its individual CHMs were non-embryotoxic, except one CHM, Amur Corktree Bark (Huang Bai, Phellodendron chinense C.K.Schneid), was weakly embryotoxic. SIT results showed that cell viability was above 50% after treatment with different concentrations of all tested CHMs. CONCLUSIONS: Our in vitro tests provided preliminary evidence for safety of the formula PHF in embryonic stem cell test and skin irritation model, but PHF shall be cautiously used in pregnant women with AD. Further studies are needed to support its clinical application as an alternative treatment for AD, especially to the patients who plan for pregnancy or at lactation stages.

Concordance of PGT for aneuploidies between blastocyst biopsies and spent blastocyst culture medium.

RESEARCH QUESTION: Non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) avoids the possible detrimental impact of invasive PGT-A on embryo development and clinical outcomes. Does cell-free DNA (cfDNA) from spent blastocyst culture medium (BCM) reflect embryonic chromosome status better than trophectoderm (TE) biopsy? DESIGN: In this study, 35 donated embryos were used for research and the BCM, TE biopsy, inner cell mass (ICM) and residual blastocyst (RB) were individually picked up from these embryos. Whole genome amplification (WGA) was performed and amplified DNA was subject to next-generation sequencing. Chromosome status concordance was compared among the groups of samples. RESULTS: The WGA success rates were 97.0% (TE biopsy), 100% (ICM), 97.0% (RB) and 88.6% (BCM). Using ICM as the gold standard, the chromosomal ploidy concordance rates for BCM, TE biopsy and RB were 58.33% (14/24), 68.75% (22/32) and 78.57% (22/28); the diagnostic concordance rates were 83.33% (20/24), 87.50% (28/32) and 92.86% (26/28); and the sex concordance rates were 92.31% (24/26), 100% (32/32) and 100% (28/28), respectively. Considering RB the gold standard, the chromosome ploidy concordance rates for BCM and TE biopsy were 61.90% (13/21) and 81.48% (22/27); the diagnostic concordance rates were 71.43% (15/21) and 88.89% (24/27); and the sex concordance rates were 91.30% (21/23) and 100% (27/27), respectively. CONCLUSIONS: The results of niPGT-A of cfDNA of spent BCM are comparable to those of invasive PGT-A of TE biopsies. Modifications of embryo culture conditions and testing methods will help reduce maternal DNA contamination and improve the reliability of niPGT-A.

Relationship between the EULAR/ACR classification criteria and organ damage in systemic lupus erythematosus.

OBJECTIVES: To study the relationship between the 2019 EULAR/ACR classification criteria and organ damage in patients with systemic lupus erythematosus (SLE). METHODS: Patients involved in a cross-sectional validation study of the EULAR/ACR criteria and judged by a panel of rheumatologists to be clinical SLE were studied. Those who fulfilled the EULAR/ACR criteria at their last clinic visit were stratified into 2 groups based on a cutoff score of 20. The last SLE International Collaborating Clinic (SLICC) Organ Damage Index (SDI) was compared between these two groups. Relationship among the domains of the EULAR/ACR criteria and SDI in all patients was studied by using Spearman's rank correlation. RESULTS: A total of 562 SLE patients were studied (93.6% women; age 36.5 ± 14.1 years; follow-up duration 11.6 ± 6.6 years). The mean and median EULAR/ACR criteria scores in those who fulfilled the EULAR/ACR criteria (N = 542) were 24.6 ± 7.3 and 24 (interquartile range 19-30), respectively. A total of 392 patients had EULAR/ACR scores of ≥20 (group 1), and 150 patients had scores of 10-19 (group 2). Group 1 patients had significantly higher prevalence of fever, alopecia, oral ulcers, acute lupus skin lesions, arthritis, serositis, seizure, hemolytic anemia, leukopenia, and renal disease and so were the anti-dsDNA, anti-Sm, antiphospholipid antibodies, and low complement state. Organ damage (SDI score of ≥1) occurred in 232 (42.8%) patients. Patients in group 1 had significantly higher SDI scores in the renal, cardiovascular, dermatological, and gonadal domains than group 2. The renal, neuropsychiatric, and antiphospholipid antibody domain scores of the EULAR/ACR criteria correlated positively with the total SDI. The renal domain of the EULAR/ACR criteria had the strongest correlation with renal damage (Rho 0.30; p < 0.001). Patients who scored 10 points in the renal domain had significantly higher renal damage score than those scored 8 points or 4 points. Gonadal damage score was also significantly more common in the 10-point than in the 8-point group. CONCLUSION: In addition to disease classification, the EULAR/ACR SLE criteria may have value in predicting prognosis.

Prevalence and risk factors of herpes zoster infection in patients with rheumatic diseases not receiving biologic or targeted therapies.

OBJECTIVES: The objective was to study the prevalence and risk factors of herpes zoster (HZ) infection in patients with rheumatic diseases. METHODS: Consecutive patients with rheumatic diseases not receiving biologic/targeted DMARDs who attended our rheumatology clinics between March and August 2019 were retrospectively reviewed. Episodes of HZ infection since their first clinic attendance were identified. Laboratory results (total white cell count, neutrophil-to-lymphocyte ratio (NLR), serum albumin, globulin, and creatinine) and use of immunosuppressive medications were compared between those with (preceding infection) and without (preceding last visit) HZ infection. Cox regression analysis was performed to identify factors associated with the first HZ infection in all patients. RESULTS: 1,479 patients were studied (88.3% women, age 45.0 ± 15.8 years). Systemic lupus erythematosus (SLE) (38.7%) and rheumatoid arthritis (28.3%) were the commonest rheumatic diseases. After a follow-up of 14,715 patient-years (9.9 ± 7.0 years), 219 (14.8%) patients developed 258 episodes of HZ infection, giving an overall prevalence of 1.75/100-patient years. The prevalence rates of HZ were highest in SLE and inflammatory myopathies (2.54 and 2.58 per 100 patient-years, respectively). Patients who experienced HZ reactivation were younger, more likely to have SLE, and had significantly lower serum albumin/globulin levels but higher NLR. Significantly more patients with HZ reactivation were using prednisolone and other immunosuppressive drugs in the visits preceding HZ infection. The cumulative risk of having HZ reactivation at 24 and 48 months was 4.9% and 7.6%, respectively. Cox regression analysis revealed that a diagnosis of SLE, increasing age, higher NLR, use of cyclophosphamide, and increasing doses of prednisolone, azathioprine, hydroxychloroquine and leflunomide were independently associated with HZ infection. CONCLUSIONS: Reactivation of HZ is fairly common in patients with rheumatic diseases. Underlying SLE, age, neutrophil/lymphocyte ratio, and immunosuppressive therapies are independent risk factors. Key Points • Herpes zoster (HZ) infection is fairly common in patients with rheumatic diseases undergoing conventional DMARD or immunosuppressive therapies. • Underlying SLE, increasing age, higher neutrophil/lymphocyte ratio and increasing dosages of immunosuppressive drugs are independent risk factors. • Patients with rheumatic diseases, particularly SLE, should be encouraged to receive HZ vaccination.

Efficacy of foldable capsular vitreous body implantation in ocular trauma and silicone oil-dependent eyes / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the clinical effect of foldable capsular vitreous body(FCVB)implantation on ocular trauma and silicone oil-dependent eyes.METHODS: A prospective case study was performed on 17 cases(17 eyes)with ocular trauma and silicone oil-dependent in the First Hospital of Changsha from October 2017 to April 2022. All patients underwent FCVB or silicone oil removal combined with FCVB implantation. The follow-up time was 6mo, and the visual acuity, intraocular pressure, ocular axes, normal external appearances and FVCB were observed at 1wk and 6mo after operation.RESULTS: Only 6 cases had visual acuity before operation, and there were no statistical differences in the visual acuity before and at 1wk and 6mo after operation(P&#x003E;0.05). The intraocular pressure was low before operation, but it was elevated at 1wk and 6mo after operation. The axial length was unchanged at 1wk and 6mo after operation, and the appearance and structure of eyeball were well maintained, and FCVB was stable with no atrophy during the follow-up period.CONCLUSIONS: FCVB implantation can preserve the appearance of eyeball, and avoid atrophy of eyeball and repeated operation, which has favorable clinical application value in the treatment of ocular trauma and silicone oil-dependent eyes.

Organizing Pneumonia in A Patient Double-Positive for ANCA and Anti-GBM Antibodies: A Case Report / 中国医学科学杂志(英文版)

Both anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are common causes of pulmonary-renal syndrome. Organizing pneumonia (OP), a special pattern of interstitial lung disease, is extremely rare either in AAV or anti-GBM disease. We report an old woman presented with OP on a background of co-presentation with both ANCA and anti-GBM antibodies.

The Efficacy and Safety of Daratumumab-Based Regimen in Treatment of Multiple Myeloma Patients with Renal Impairment / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI).@*METHODS@#The clinical data of 15 MM patients with RI who received daratumumab-based regimen from January 2021 to March 2022 in three centers were retrospectively analyzed. Patients were treated with daratumumab or daratumumab combined with dexamethasone or daratumumab combined with bortezomib and dexamethasone and the curative effect and survival were analyzed.@*RESULTS@#The median age of 15 patients was 64 (ranged 54-82) years old. Six patients were IgG-MM, 2 were IgA-MM,1 was IgD-MM and 6 were light chain MM. Median estinated glomerular filtration rate (eGFR) was 22.48 ml/(min·1.73 M2). Overall response rate of 11 patients with MM was 91% (≥MR), including 1 case of stringent complete response (sCR), 2 cases of very good partial response (VGPR), 3 cases of partial response (PR) and 4 cases of minor response (MR). The rate of renal response was 60%(9/15), including 4 cases of complete response (CR), 1 case of PR and 4 cases of MR. A median time of optimal renal response was 21 (ranged 7-56) days. With a median follow-up of 3 months, the median progression-free survival and overall survival of all patients were not reached. After treatment with daratumumab-based regimen, grade 1-2 neutropenia was the most common hematological adverse reaction. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections.@*CONCLUSION@#Daratumumab-based regimens have good short-term efficacy and safety in the treatment of multiple myeloma patients with renal impairment.

Family environment characteristics and sleep duration in children: Maternal mental health as a mediator.

BACKGROUND: Family environment is a key factor affecting children's health. However, little is known about whether and how the family environment affects sleep duration in children. This study investigated the effects of both physical and social characteristics of the family environment on sleep duration in children and determined whether these associations were mediated by maternal mental health. METHODS: Data were obtained from the Taiwan Birth Cohort Study. A total of 19,400 children who completed 6-month, 18-month, 3-year, 5.5-year, and 8-year surveys were analyzed. The physical family environment characteristics were household crowding and housing quality. Family functioning was used as an indicator of family social environment. Multiple linear regression and path analysis were performed to test the hypotheses. RESULTS: The children living in crowded households had shorter sleep durations (ß = -0.03, p < .001). Superior housing quality and family functioning were associated with longer sleep durations (ß = 0.04 and 0.02, respectively, ps < .01). The effects of housing quality and family functioning on sleep duration were mediated by maternal mental health. CONCLUSIONS: Both physical and social characteristics of the family environment are critical to sleep duration in children. The effects of family environment characteristics on sleep duration in children are in part mediated by maternal mental health. Interventions to improve sleep during childhood by targeting the family environment may be more effective when maternal mental health is considered.

Childhood Handwashing Habit Formation and Later COVID-19 Preventive Practices: A Cohort Study.

OBJECTIVE: This study identified developmental patterns of handwashing habit formation during childhood and examined their associations with later COVID-19 preventive practices. METHODS: We used data from the Taiwan Birth Cohort Study, which included 11,254 adolescents with complete data on childhood handwashing behavior and age-15 COVID-19 survey items. Bias-adjusted 3-step latent class analysis was used to test study hypotheses. RESULTS: The rates of handwashing and mask-wearing during the pandemic were 63.8% and 93.8%, respectively. Five distinct patterns of handwashing habit formation were identified: early formation (14.89%), delayed formation (17.73%), gradual formation (42.98%), inconsistent formation (9.78%), and nonformation (14.62%). Compared with adolescents with an early formation pattern of handwashing habits, those with other patterns exhibited lower odds ratios (ORs) of handwashing during COVID-19; these ORs were 0.67 (95% confidence interval [CI], 0.49-0.85), 0.60 (95% CI, 0.44-0.77), 0.29 (95% CI, 0.08-0.49), and 0.21 (95% CI, 0.01-0.40) for those with delayed formation, gradual formation, inconsistent formation, and nonformation patterns, respectively. Moreover, relative to that of adolescents with the early formation pattern, mask-wearing was less common among adolescents with gradual formation, inconsistent formation, and nonformation patterns, with ORs of 0.54 (95% CI, 0.16-0.92), 0.50 (95% CI, 0.03-0.96), and 0.26 (95% CI, 0.00-0.65), respectively. CONCLUSIONS: The early formation of hygienic habits is associated with higher adherence to pandemic preventive practices among adolescents. Our findings suggest that interventions to promote hygienic behaviors can start as early as age 3 through the introduction of healthy habits such as handwashing.

Validation of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in ANA-positive Chinese patients.

Background: The aim of this study was to validate the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) in antinuclear antibody (ANA)-positive Chinese patients. Methods: Medical records of all adult patients who attended the rheumatology out-patient clinics between May and September 2019 were reviewed. Patients with ever ANA positive (titre ⩾1:80) were included and evaluated for the fulfilment of the 2019 EULAR/ACR, 2012 Systemic Lupus International Collaborating Clinics (SLICC) and 1997 ACR criteria for SLE classification. The performance of these criteria in predicting a clinical diagnosis of SLE as judged by an independent panel of rheumatologists was studied and compared in different subgroups. Results: A total of 1533 patients (88.2% women; age at first clinic attendance 45.5 ± 15.6 years) were studied and 562 patients were judged to be clinical SLE. The sensitivity and specificity of the EULAR/ACR (⩾10 points), SLICC and ACR criteria for a clinical diagnosis of SLE was 96.1%, 97.9% and 86.1%; and 85.8%, 86.3% and 94.3%, respectively. Applying the attribution rule to the non-SLE controls, the specificity of the three criteria increased to 95.0%, 92.5% and 98.8%, respectively. The specificity of the EULAR/ACR criteria was higher in male patients (97.9%), those aged >50 years (97.0%) and disease duration of ⩽3 years (97.6%). Using a cut-off of 12 points, the specificity of the EULAR/ACR criteria was further increased (96.6%) while a high sensitivity (95.0%) was maintained. Conclusion: In Chinese patients with a positive ANA, the EULAR/ACR criteria for clinical SLE perform equally well to the SLICC criteria. Both the EULAR/ACR and SLICC are more sensitive but less specific than the ACR criteria. The specificity of all the three criteria is enhanced by applying the attribution rule to controls. The specificity of the EULAR/ACR criteria is higher in certain patient subgroups or when the cut-off score is raised.