Distinct characteristics of the gut virome in patients with osteoarthritis and gouty arthritis.

BACKGROUND/PURPOSE(S): The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. METHODS: We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. RESULTS: Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. CONCLUSION: Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies.

Synergistic Radiation Effects in PPD CMOS Image Sensors Induced by Neutron Displacement Damage and Gamma Ionization Damage.

The synergistic effects on the 0.18 µm PPD CISs induced by neutron displacement damage and gamma ionization damage are investigated. The typical characterizations of the CISs induced by the neutron displacement damage and gamma ionization damage are presented separately. The CISs are irradiated by reactor neutron beams up to 1 × 1011 n/cm2 (1 MeV neutron equivalent fluence) and 60Co γ-rays up to the total ionizing dose level of 200 krad(Si) with different sequential order. The experimental results show that the mean dark signal increase in the CISs induced by reactor neutron radiation has not been influenced by previous 60Co γ-ray radiation. However, the mean dark signal increase in the CISs induced by 60Co γ-ray radiation has been remarkably influenced by previous reactor neutron radiation. The synergistic effects on the PPD CISs are discussed by combining the experimental results and the TCAD simulation results of radiation damage.

Integrating plant physiology into simulation of fire behavior and effects.

Wildfires are a global crisis, but current fire models fail to capture vegetation response to changing climate. With drought and elevated temperature increasing the importance of vegetation dynamics to fire behavior, and the advent of next generation models capable of capturing increasingly complex physical processes, we provide a renewed focus on representation of woody vegetation in fire models. Currently, the most advanced representations of fire behavior and biophysical fire effects are found in distinct classes of fine-scale models and do not capture variation in live fuel (i.e. living plant) properties. We demonstrate that plant water and carbon dynamics, which influence combustion and heat transfer into the plant and often dictate plant survival, provide the mechanistic linkage between fire behavior and effects. Our conceptual framework linking remotely sensed estimates of plant water and carbon to fine-scale models of fire behavior and effects could be a critical first step toward improving the fidelity of the coarse scale models that are now relied upon for global fire forecasting. This process-based approach will be essential to capturing the influence of physiological responses to drought and warming on live fuel conditions, strengthening the science needed to guide fire managers in an uncertain future.

Regulation of Vicia faba L. Response and Its Effect on Megoura crassicauda Reproduction under Zinc Stress.

The heavy metal zinc (Zn) is known to be transmitted in the food chain; however, the effect of Zn stress on beans and herbivorous insects is largely unclear. This study aimed to investigate the resistance of broad bean plants to Zn stress and the consequent changes in their physiological and biochemical metabolism by simulating heavy metal pollution in soil. Simultaneously, the effects of aphid progeny treated with different Zn concentrations on the expression of carbohydrate and related genes were analyzed. The results showed that Zn had no effect on the germination rate of broad beans, but other effects mainly manifested as follows. (1) Chlorophyll content decreased. (2) The total soluble sugar and Zn content in stems and leaves increased with increasing Zn content. (3) The proline content first increased and then decreased with increasing Zn content. (4) The height of the seedlings indicates that low concentrations promote growth and high concentrations inhibit growth. In addition, only the first-generation fecundity decreased significantly when aphids fed on heavy metal broad beans. Continuous high Zn levels increase the trehalose content of aphid F1 and F2, while F3 decreases. These results can not only provide a theoretical basis for exploring the impact of soil heavy metal pollution on ecosystems but also preliminarily evaluate the possibility of broad beans as a means of pollution remediation.

Detection of Antibiotic Resistance in Feline-Origin ESBL Escherichia coli from Different Areas of China and the Resistance Elimination of Garlic Oil to Cefquinome on ESBL E. coli.

The development of drug-resistance in the opportunistic pathogen Escherichia coli has become a global public health concern. Due to the share of similar flora between pets and their owners, the detection of pet-origin antibiotic-resistant E. coli is necessary. This study aimed to detect the prevalence of feline-origin ESBL E. coli in China and to explore the resistance elimination effect of garlic oil to cefquinome on ESBL E. coli. Cat fecal samples were collected from animal hospitals. The E. coli isolates were separated and purified by indicator media and polymerase chain reaction (PCR). ESBL genes were detected by PCR and Sanger sequencing. The MICs were determined. The synergistic effect of garlic oil and cefquinome against ESBL E. coli was investigated by checkerboard assays, time-kill and growth curves, drug-resistance curves, PI and NPN staining, and a scanning electronic microscope. A total of 80 E. coli strains were isolated from 101 fecal samples. The rate of ESBL E. coli was 52.5% (42/80). The prevailing ESBL genotypes in China were CTX-M-1, CTX-M-14, and TEM-116. In ESBL E. coli, garlic oil increased the susceptibility to cefquinome with FICIs from 0.2 to 0.7 and enhanced the killing effect of cefquinome with membrane destruction. Resistance to cefquinome decreased with treatment of garlic oil after 15 generations. Our study indicates that ESBL E. coli has been detected in cats kept as pets. The sensitivity of ESBL E. coli to cefquinome was enhanced by garlic oil, indicating that garlic oil may be a potential antibiotic enhancer.

[Cost-effectiveness analysis of Chaiyin Granules in treatment of influenza].

This study aimed to evaluate the cost-effectiveness of Chaiyin Granules compared with Oseltamivir Phosphate Capsules in the treatment of influenza(exogenous wind-heat syndrome). Based on a randomized, double-blind, positive drug parallel control clinical trial, this study evaluated the pharmacoeconomics of Chaiyin Granules with cost-effectiveness analysis method. A total of 116 patients with influenza from eight hospitals(grade Ⅱ level A above) in 6 cities were selected in this study, including 78 cases in the experimental group with Chaiyin Granules and Oseltamivir Phosphate Capsules placebo, and 38 cases in the control group with Oseltamivir Phosphate Capsules and Chaiyin Granules placebo. The total cost of this study included direct medical cost, direct non-medical cost, and indirect cost. The remission time of clinical symptoms, cure time/cure rate, antipyretic onset time/complete antipyretic time, viral nucleic acid negative rate, and traditional Chinese medicine(TCM) syndrome curative effect were selected as the effect indicators for cost-effectiveness analysis. Four-quadrant diagram was used to estimate the incremental cost-effectiveness ratio. The results showed that Chaiyin Granules were not inferior to Oseltamivir Phosphate Capsules in the remission time of clinical symptoms of influenza(3.1 d vs 2.9 d, P=0.360, non-inferiority margin was 0.5 d). Compared with Oseltamivir Phosphate Capsules, Chaiyin Granules would delay the remission time of clinic symptoms of influenza for 1 d, but could save 213.9 yuan. 1 d delay in cure time could save 149.3 yuan; 1% reduction in the cure rate could save 8.2 yuan; 1 d delay in antipyretic onset time could save 295.4 yuan; 1 d delay in complete antipyretic time could save 114.3 yuan; 1% reduction in the 5-day cure rate of TCM syndrome could save 19.2 yuan. Different from other indicators, there was no statistically significant difference between two groups in the effect of negative conversion rate of viral nucleic acid, but the cost was lower and the effect was superior, and the pharmacoeconomics was not different from that of Oseltamivir Phosphate Capsules in the field of influenza treatment.

Genome-wide identification and expression analysis of carotenoid cleavage oxygenase genes in Litchi (Litchi chinensis Sonn.).

BACKGROUND: Carotenoid cleavage oxygenases (CCOs) include the carotenoid cleavage dioxygenase (CCD) and 9-cis-epoxycarotenoid (NCED), which can catalize carotenoid to form various apocarotenoids and their derivatives, has been found that play important role in the plant world. But little information of CCO gene family has been reported in litchi (Litchi chinensis Sonn.) till date. RESULTS: In this study, a total of 15 LcCCO genes in litchi were identified based on genome wide lever. Phylogeny analysis showed that LcCCO genes could be classified into six subfamilies (CCD1, CCD4, CCD7, CCD8, CCD-like, and NCED), which gene structure, domain and motifs exhibited similar distribution patterns in the same subfamilies. MiRNA target site prediction found that there were 32 miRNA target sites in 13 (86.7%) LcCCO genes. Cis-elements analysis showed that the largest groups of elements were light response related, following was plant hormones, stress and plant development related. Expression pattern analysis revealed that LcCCD4, LcNCED1, and LcNCED2 might be involving with peel coloration, LcCCDlike-b might be an important factor deciding fruit flavor, LcNCED2 and LcNCED3 might be related to flower control, LcNCED1 and LcNCED2 might function in fruitlet abscission, LcCCD4a1, LcCCD4a2, LcCCD1, LcCCD4, LcNCED1, and LcNCED2 might participate in postharvest storage of litchi. CONCLUSION: Herein, Genome-wide analysis of the LcCCO genes was conducted in litchi to investigate their structure features and potential functions. These valuable and expectable information of LcCCO genes supplying in this study will offer further more possibility to promote quality improvement and breeding of litchi and further function investigation of this gene family in plant.

Propofol affects mouse embryonic fibroblast survival and proliferation in vitro via ATG5- and calcium-dependent regulation of autophagy.

Propofol is a commonly used intravenous anesthetic agent, which has been found to affect cell survival and proliferation especially in early life. Our previous studies show that propofol-induced neurodegeneration and neurogenesis are closely associated with cell autophagy. In the present study we explored the roles of autophagy-related gene 5 (ATG5) in propofol-induced autophagy in mouse embryonic fibroblasts (MEF) in vitro. We showed that ATG5 was functionally related to propofol-induced cell survival and damage: propofol significantly enhanced cell survival and proliferation at a clinically relevant dose (10 µM), but caused cell death at an extremely high concentration (200 µM) in ATG5-/- MEF, but not in WT cells. The dual effects found in ATG5-/- MEF could be blocked by intracellular Ca2+ channel antagonists. We also found that propofol evoked a moderate (promote cell growth) and extremely high (cause apoptosis) cytosolic Ca2+ elevation at the concentrations of 10 µM and 200 µM, respectively, only in ATG5-/- MEF. In addition, ATG5-/- MEF themselves released more Ca2+ in cytosolic space and endoplasmic reticulum compared with WT cells, suggesting that autophagy deficiency made intracellular calcium signaling more vulnerable to external stimuli (propofol). Altogether, our results reveal that ATG5 plays a crucial role in propofol regulation of cell survival and proliferation by affecting intracellular Ca2+ homeostasis.

A single-dose of stellate ganglion block for the prevention of postoperative dysrhythmias in patients undergoing thoracoscopic surgery for cancer: A randomised controlled double-blind trial.

BACKGROUND: New-onset arrhythmias and sleep disturbances are frequently observed during the postoperative period in patients undergoing thoracic surgery. OBJECTIVE: We evaluated the effectiveness of a single-dose stellate ganglion block (SGB) to prevent the occurrence of arrhythmias in patients undergoing thoracic surgery for cancer. DESIGN: Randomised controlled double-blind study. SETTING: Single university hospital. PATIENTS: Ninety patients with lung cancer or oesophagal cancer scheduled for elective video-assisted thoracoscopic surgery were randomly randomised into one of two equal groups (the SGB group and control group, n = 40 each). INTERVENTIONS: Patients received a single dose of 5 ml of 0.5% ropivacaine during ultrasound-guided SGB before induction of general anaesthesia in the SGB group. MAIN OUTCOME MEASURES: Holter ECG was continuously monitored during the first 48 postoperative hours, and sleep state was monitored during the first two postoperative nights. RESULTS: The incidences of postoperative supraventricular tachycardias were lower in the SGB group compared with the control group during the first 48 postoperative hours; 11.6 (5/43) vs. 31.8% (14/44), respectively, P = 0.023 (odds ratio 0.28, 95% confidence interval 0.09 to 0.87). The SGB also prolonged the total sleep time and increased the sleep efficiency during the first two postoperative nights. The duration of stage N2 sleep was longer in the SGB group compared with the control group [28 (interquartile range, 14 to 58) to 94 (interquartile range, 69 to 113) min, P = 0.016] on the first postoperative night. There were no differences in the duration of stage N1 and N3 sleep (P = 0.180, 0.086, respectively) on the first postoperative night, and the duration of stage N1, N2 and N3 sleep (P = 0.194, 0.057, 0.405, respectively) on the second postoperative night between the groups. CONCLUSION: A pre-operative SGB effectively prevented the occurrence of postoperative supraventricular tachycardias and improves the objective sleep quality in patients undergoing thoracic surgery for cancer. TRIAL REGISTRATION NUMBER: ChiCTR-1900023064.

Expert Recommendations for Tracheal Intubation in Critically ill Patients with Noval Coronavirus Disease 2019.

Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), is a highly contagious disease. It firstly appeared in Wuhan, Hubei province of China in December 2019. During the next two months, it moved rapidly throughout China and spread to multiple countries through infected persons travelling by air. Most of the infected patients have mild symptoms including fever, fatigue and cough. But in severe cases, patients can progress rapidly and develop to the acute respiratory distress syndrome, septic shock, metabolic acidosis and coagulopathy. The new coronavirus was reported to spread via droplets, contact and natural aerosols from human-to-human. Therefore, high-risk aerosol-producing procedures such as endotracheal intubation may put the anesthesiologists at high risk of nosocomial infections. In fact, SARS-CoV-2 infection of anesthesiologists after endotracheal intubation for confirmed COVID-19 patients have been reported in hospitals in Wuhan. The expert panel of airway management in Chinese Society of Anaesthesiology has deliberated and drafted this recommendation, by which we hope to guide the performance of endotracheal intubation by frontline anesthesiologists and critical care physicians. During the airway management, enhanced droplet/airborne PPE should be applied to the health care providers. A good airway assessment before airway intervention is of vital importance. For patients with normal airway, awake intubation should be avoided and modified rapid sequence induction is strongly recommended. Sufficient muscle relaxant should be assured before intubation. For patients with difficult airway, good preparation of airway devices and detailed intubation plans should be made.

[Effects of Jinwu Jiangu recipe on IL-17/STAT3 signals in rheumatoid arthritis synoviocytes].

This paper aimed to investigate the effects of Jinwu Jiangu recipe total extract on the IL-17/STAT3 signals in rheumatoid arthritis synovial fibroblasts(RASF). The primary RASFs were cultured by tissue piece method in vitro， and divided into blank control group， Jinwu Jiangu recipe low dose group， Jinwu Jiangu recipe middle dose group， Jinwu Jiangu recipe high dose group， and tripterygium glycosides control group. They were then treated with corresponding serum free medium， different doses of Jinwu Jiangu recipe total extract(0.06， 0.6， 6.0 g·L⁻¹)， and tripterygium glycosides(0.03 g·L⁻¹) respectively for 24 hours. The gene expression levels of RORα， RORγt， and STAT3 mRNA were detected by polymerase chain reaction(PCR)， and the protein activity of IL-17R and pSTAT3 were measured by Western blot assay. The results showed that as compared with blank control group， the expression levels of RORα， RORγt， IL-17R and STAT3 mRNA in RASF were significantly declined(P<0.01). As compared with tripterygium glycosides control group， Jinwu Jiangu recipe total extract middle dose group and high dose group can down-regulate the expression levels of RORα， RORγt， IL-17R and STAT3 mRNA(P<0.05)， and the effect was more obvious in high dose group(P<0.01). As compared with blank control group， the protein expression levels of IL-17R and pSTAT3 in each treatment group were obviously decreased(P<0.01). As compared with tripterygium glycosides control group， Jinwu Jiangu recipe high dose group had more obvious effect in down-regulating the protein expression of pSTAT3(P<0.01). Therefore， Miao medicine Jinwu Jiangu recipe total extract can down-regulate the expressions of RORα， RORγt， and STAT3 mRNA， and inhibit the protein activity of IL-17R and pSTAT3 in RASF.

[Effect of Jinwu Jiangu Recipe on Expressions of NF-kappaB and IL-17 in Collagen Induced Arthritis Model Rats].

OBJECTIVE: To explore the effect of Jinwu Jiangu Recipe (JJR) on the expression of synovial cells' nuclear factor-kappaB (NF-kappaB) and serum interleukin 17 (IL-17) in collagen induced arthritis (CIA) rats. METHODS: Totally 60 Wistar rats were randomly divided into 6 groups, i.e., the blank control group, the model group, high, middle, and low dose JJR treatment groups, and the tripterygium control group, 10 in each group. Except rats in the blank control group, CIA model was established in rats of the rest 5 groups. Then they were treated from the 7th day of modeling. After 4 weeks of medication they were sacrificed, serum collected, and synovium of joints were isolated. The expression of serum IL-17 was detected in synovium of joints by enzyme linked immunosorbent assay (ELISA). And the expression of NF-kappaB/P65, Ikappabetaalpha and NF-KappaB/P50 were detected by Western blot. RESULTS: Compared with the blank control group, the serum IL-17 level increased in the model group (P <0. 01). Compared with the model group, the serum IL-17 level obviously decreased in high and middle dose JJR groups and the tripterygium control group (P < 0.01). Results of Western blot showed, when compared with the blank control group, protein activities of NF-kappaB/P65 and NF-kappaB/P50 were significantly enhanced in the model group (P < 0.01). Compared with the model group, protein activities of NF-kappaB/P65 and NF-kappaB/P50 significantly decreased in high and middle dose JJR groups and the tripterygium control group (P < 0.05, P < 0.01). All indices mentioned above were higher in the low dose JJR group than in the tripterygium control group (P < 0.05, P < 0.01). CONCLUSION: JJR could lower the expression of serum IL-17 in CIA model rats, and inhibit protein activities of NF-kappaB/P65 and NF-kappaB/P50.

Androgenic regulation of beta-defensins in the mouse epididymis.

BACKGROUND: The majority of beta-defensin family members are exclusively expressed in the epididymis, and some members have been shown to play essential roles in sperm maturation and fertility in rats, mice and humans. Therefore, beta-defensins are hypothesized to be potential targets for contraception and infertility diagnosis and treatment. Clarifying the regulatory mechanisms for the expression of these genes is necessary. Androgen/androgen receptor (AR) signaling plays an important regulatory role in epididymal structure and function. However, very little is known about the androgenic regulation on the production and secretion of the epididymal beta-defensins. METHODS: The expression of beta-defensins was detected by quantitative RT-PCR. The androgen dependence of beta-defensins was determined by bilateral orchiectomy and androgen supplementation. The androgen response elements (AREs) in the promoters of beta-defensins were identified using the MatInspector software. The binding of AR to AREs was assayed by ChIP-PCR/qPCR. RESULTS: We demonstrated that 23 mouse caput epididymal beta-defensins were differentially regulated by androgen/androgen receptor. Six genes, Defb18, 19, 20, 39, 41, and 42, showed full regulation by androgens. Ten genes, Defb15, 30, 34, 37, 40, 45, 51, 52, 22 and Spag11a, were partially regulated by androgens. Defb15, 18, 19, 20, 30, 34, 37, 39, 41, 42, 22 and Spag11a were associated with androgen receptor binding sites in their promoter or intronic regions, indicating direct regulation of AR. Six genes, Defb1, 12, 13, 29, 35, and spag11b/c, exhibited an androgen-independent expression pattern. One gene, Defb25, was highly dependent on testicular factors rather on androgens. CONCLUSIONS: The present study provides novel insights into the mechanisms of androgen regulation on epididymal beta-defensins, enabling a better understanding of the function of beta-defensins in sperm maturation and fertility.

[Chinese medical syndromes of rheumatoid arthritis: a clinical literature study].

OBJECTIVE: To explore the distribution features of Chinese medical syndromes of rheumatoid arthritis (RA) by literature retrieval. METHODS: Pertinent articles on treating RA by syndrome differentiation were retrieved from China National Knowledge Infrastructure Databases (CNKI), VIP Chinese Biomedical Journal Database, Guizhou Digital Library, and Duxiu Chinese Academic Periodicals full papers database from January 2000 to December 2011. RESULTS: A total of 33 documents were recruited covering 4 233 cases. Damp-heat blocking collaterals syndrome occupied the top in the occurrence frequency (20 times, 60.61%), followed by deficiency of Gan and Shen syndrome (18 times, 54.55%), intermingled phlegm and blood-stasis syndrome (17 times, 51.52%), wind-cold-damp impediment syndrome (15 times, 45.45%), cold-damp blocking collaterals syndrome (14 times, 42.42%), wind-damp-heat impediment and deficiency of qi and blood syndrome (10 times, 30.30%), and intermingled cold and heat syndrome (9 times, 27.27%). According to the case number of patients, it was sequenced as damp-heat blocking collaterals syndrome syndrome (768 cases, 18.14%), wind-damp-heat impediment syndrome(666 cases, 15.73%), wind-cold-damp impediment syndrome(584 cases, 13.80%), cold-damp blocking collaterals syndrome syndrome (517 cases, 12.21%), intermingled cold and heat syndrome (415 cases, 9.80%), intermingled phlegm and blood-stasis syndrome (364 cases, 8.60%), deficiency of Gan and Shen syndrome (235 cases, 5.55%),asthenia of healthy energy due to lingering arthralgia syndrome (223 cases, 5.27%). The case numbers of remaining syndromes did not exceed 5%. CONCLUSION: Damp-heat blocking collaterals syndrome was the main syndrome in RA patients, followed by wind-cold-damp impediment syndrome,wind-damp-heat impediment syndrome,cold-damp blocking collaterals syndrome,intermingled phlegm and blood-stasis syndrome, and deficiency of Gan and Shen syndrome.

Safety and anatomical outcome analysis after flow diverter coverage of the anterior cerebral artery.

OBJECTIVES: Few studies on ischemic complications and flow changes after a flow diverter covering the anterior cerebral artery. The purpose of the study was to explore the ischemic complications and anatomical alterations associated with the flow diverter after it covers the anterior cerebral artery. MATERIALS AND METHODS: In this single-center study, patients treated with FD covering the anterior cerebral artery at the First Affiliated Hospital of Zhengzhou University were retrospectively collected. The primary endpoint was ischemic complications related to the anterior cerebral artery. Secondary endpoints were anatomical changes in the anterior cerebral artery postoperatively and at follow-up. RESULTS: A total of 59 patients were included in this study. Four (6.8%) patients presented with ischemic stroke symptoms. Immediately after the procedure, complete occlusion of A1 and decreased blood flow was observed in 13 (22.0%) and 21 patients (35.6%), respectively. At follow-up, A1 artery was occluded in 34 patients (57.6%) and decreased blood flow was observed in 10 patients (16.9%). Symptoms of neurological deficits related to the anterior cerebral artery were not observed in all patients at follow-up. CONCLUSION: Coverage of A1 is safe, with a low incidence of ischemic stroke, when using an FD to treat aneurysms. Risk of reduced perfusion of the anterior cerebral artery postoperatively even if the anterior communicating artery is open. In cases with A1 occlusion, the blood flow in the distal the anterior cerebral artery can be adequately compensated by opening the anterior communicating artery and good vascular anastomoses.

Hydroxychloroquine-induced hyperpigmentation of the skin and bull's-eye maculopathy in rheumatic patients: a case report and literature review.

Hydroxychloroquine (HCQ) is used as a traditional disease-modifying antirheumatic drugs (DMARDs), for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, it can cause serious adverse reactions, including hyperpigmentation of the skin and bull's-eye macular lesions. Here, we present a case of HCQ-induced hyperpigmentation of the skin and bull's-eye macular lesions in a patient who received HCQ for RA. A 65-year-old female patient developed blurred vision and hyperpigmentation of multiple areas of skin over the body for one month after 3 years of HCQ treatment for RA. Based on clinical presentation, ophthalmological examination and dermatopathological biopsy, a diagnosis of drug-induced cutaneous hyperpigmentation and bullous maculopathy of the right eye was made. After discontinuation of HCQ and treatment with iguratimod tablets, the hyperpigmentation of the patient 's skin was gradually reduced, and the symptoms of blurred vision were not significantly improved. We also reviewed the available literature on HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions and described the clinical features of HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions. In conclusion, clinicians should be aware of early cutaneous symptoms and HCQ-associated ophthalmotoxicity in patients with rheumatic diseases on HCQ sulphate and should actively monitor patients, have them undergo regular ophthalmological examinations and give appropriate treatment to prevent exacerbation of symptoms.

Efficacy of adalimumab combined with Tripterygium wilfordii Hook F in the treatment of patient with rheumatoid arthritis: A multicenter, open-label, randomized-controlled trial.

OBJECTIVES: To evaluate the efficacy and safety of adalimumab (ADA) combined with Tripterygium wilfordii Hook F (TwHF) in the treatment of methotrexate (MTX)-inadequate response patients with rheumatoid arthritis (RA). METHODS: In this multicenter, open-label, randomized controlled clinical trial, 64 RA patients with inadequate response to MTX were 1:1 randomly assigned into treatment or control groups. The treatment group was treated with ADA in combination with TwHF, and the control group was treated with ADA in combination with MTX for 24 weeks. The primary endpoint was the percentage of patients having low disease activity (2.6 ≤ DAS28-ESR < 3.2) and remission rates (DAS28-ESR < 2.6) at week 24. RESULTS: In total, 53 of the 64 patients (82.8%) completed this 24-week clinical trial. By intent-to-treat (ITT) analysis, a comparable outcome was observed between the two groups. The percentage of patients achieving low disease activity in the treatment group and control group were 43.8% and 46.9% (95% CI, 21.28 to 27.48, p = .802). Percentage of patients achieving low disease activity rates were respectively 28.1% and 31.3% in the treatment group and control group (95% CI, 19.18 to 25.58, p = .784). In per-protocol (PP) analysis, the results were consistent with the ITT model. The incidence of adverse events was comparable between the two groups. CONCLUSIONS: There were no significant differences in efficacy and safety between ADA combined with TwHF versus ADA combined with MTX in the treatment of RA. TwHF might be an alternative treatment for RA patients who are intolerant to MTX.

Different effects of androgen on the expression of Fut1, Fut2, Fut4 and Fut9 in male mouse reproductive tract.

The α-(1,2) fucosyltransferases (Fut1 and Fut2) and α-(1,3) fucosyltransferases (Fut4, Fut9) are responsible for the synthesis of Lewis X (LeX) and Lewis Y (LeY) conjugated to glycoproteins. We recently reported that these fucosyltransferases were differentially expressed in the reproductive tract of male mouse. Here, we studied the effect of androgen on fucosyltransferase expression through the use of mouse castration models. We found that Fut1 mRNA and Fut4 mRNA were upregulated, while Fut2 mRNA and Fut9 mRNA were downregulated by androgen in the caput epididymis. However, in the vas deferens and prostate, only Fut4 mRNA and Fut2 mRNA were respectively upregulated following exposure to androgen. In the seminal vesicle, all fucosyltransferases, with the exception of Fut9, were upregulated. We identified the androgen receptor binding sites (ARBSs) of Fut2, Fut4 and Fut9 in the caput epididymis. Luciferase assay for these ARBSs is able to provide an indication as to why Fut4 and Fut9 are differently expressed and regulated by androgen, although they catalyze the same α-(1,3) fucose linkage. Our study showed that androgen could differentially regulate the expression of these fucosyltransferases and provided an insight into the characteristic distribution of each fucosyltransferase responsible for LeX/LeY biosynthesis in the male reproductive tract.