bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastrointestinal bleeding after endoscopic mucosal resection in a case of Peutz–Jeghers syndrome with hypofibrinogenemia: A case report
Authors: Kakiuchi Toshihiko , Takedomi Hironobu , Akutagawa Takashi , Tsuruoka Nanae , Sakata Yasuhisa , Matsuo Muneaki
Published: October 2022

Backgroud

Peutz–Jegers syndrome (PJS) is an autosomal dominant hereditary disorder characterized by hamartomatous polyposis of the entire gastrointestinal tract. Fibrinogen (Fbg) is synthesized by the liver, and hypofibrinogenemia is often asymptomatic and manifests with bleeding after trauma or invasive surgical procedures. Here, we present a case of a pediatric patient with PJS and hypofibrinogenemia who manifested with gastrointestinal bleeding after endoscopic mucosal resection (EMR) of small intestinal polyps.

Case Presentation

An 11-year-old boy with PJS was referred to our hospital. Since his mother was diagnosed with PJS, with black pigments being observed on his lips, mouth, and limbs, he underwent upper and lower gastrointestinal endoscopy at the age of 8 years at a previous hospital. EMR for duodenal polyp was performed, and the pathological findings were consistent with hamartoma. His Fbg level was 117 mg/dl at the time, with no post-bleeding being detected after EMR. The small intestine was not assessed at the prior facility and was left neglected for three years. At our hospital, small intestine fluoroscopy was performed and revealed a polyp in the jejunum, and abdominal computed tomography showed two polyps and intussusception. On double-balloon enteroscopy, the resected polyps were hamartoma with diameters of 20 and 30 mm. The patient’s Fbg level was 107 mg/dl. The day after EMR, he had melena and black stools. He was diagnosed with post-EMR bleeding and started to stop eating, and hemostatic agents were given. His hemoglobin level dropped to 9.2 g/dl the next day. Genetic testing for congenital Fbg deficiency revealed a heterozygous pathogenic variant in fibrinogen gamma chain Exon 10. Therefore, he was diagnosed with concurrent hypofibrinogenemia and PJS.

Conclusion

To the best of our knowledge, this is the first reported case with concurrent PJS and hypofibrinogenemia. In patients with PJS, hypofibrinogenemia should be considered as one of the risk factors of postoperative bleeding during polypectomy, and appropriate prophylactic measures should be taken.
Vitamin D levels and Vitamin D-related gene polymorphisms in Chinese children with type 1 diabetes
Authors: Chen Xiaofang , Fu Jia , Qian Ying , Zhi Xiufang , Pu Linjie , Gu Chunyu , Shu Jianbo , Lv Ling , Cai Chunquan
Published: October 2022

Low vitamin D levels may play a role in type 1 diabetes (T1D) susceptibility. Since 25(OH)D synthesis is genetically regulated, single nucleotide polymorphisms (SNPs) of important genes have also been shown to modulate the risk of T1D, so this study aimed to investigate the relationship between five SNPs in CYP2R1, DHCR7, CYP24A1, VDR genes, serum 25(OH)D levels and T1D in Chinese children. This case-control study included 141 T1D patients and 200 age-matched healthy children.25 (OH) D concentration was determined, genotyping was performed by High resolution melting (HRM). There was a significant difference in the prevalence of vitamin D deficiency, insufficiency, and sufficiency between T1D and healthy controls. (χ2 = 10.86, p = 0.004), however no evidence of the association between any group of SNPs and circulating 25(OH) D levels was observed. The allele distribution of CYP2R1(rs1993116) was significantly different between T1D and control group (p = 0.040), and the C allele carriers of rs1993116 had a higher risk of T1D than the T allele carriers, Carriers of the CC and CT genotypes of rs1993116 have higher T1D risk than those carrying the TT genotype. GMDR analysis revealed a significant interaction between CYP2R1(rs12794714) and CYP2R1(rs1993116) in the risk of T1D with a maximum testing balance accuracy of 60.39%.
Effects of Poria cocos extract on metabolic dysfunction-associated fatty liver disease via the FXR/PPARα-SREBPs pathway
Authors: He Jinbiao , Yang Yu , Zhang Fan , Li Yanjuan , Li Xiaosi , Pu Xuemei , He Xudong , Zhang Mei , Yang Xinxing , Yu Qiuman , Qi Yan , Li Xuefang , Yu Jie
Published: October 2022

Despite the increase in the global prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD), no approved drug currently exists for the disease. Poria cocos (Schw.) Wolf (P. cocos) is a medicinal mushroom belonging to a family of polyporaceae widely used in TCM clinics to protect the liver and treat obesity. However, its efficacy, practical components, and underlying mechanism against MAFLD are yet to be determined. In this study, we evaluated the effects of Poria cocos (P. cocos) ethanol extract (EPC) on hepatic dyslipidemia, steatosis, and inflammation by both bioinformatics analysis and MAFLD rats induced by HFD feeding. We found EPC treatment dramatically reduced lipid accumulation, inflammatory cell infiltration, and liver injury. EPC reduced serum TC, TG levels, and hepatic TG, TBA, and NEFA contents. UHPLC Q-Trap/MS examination of BA profiles in serum and feces showed that EPC increased fecal conjugated BAs, decreased free BAs, and improved BA metabolism in HFD-fed rats. Western blot and RT-qPCR analysis showed that EPC could activate hepatic FXR and PPARα expression and reduce CYP7A1 and SREBP-1c expression. Systemic pharmacology combined with molecular docking suggested that poricoic acid B and polyporenic acid C, the major active compounds in EPC, could ameliorate lipid homeostasis by activating the nuclear receptor PPARα. We further confirmed their inhibition effects of lipid droplet deposition in steatized L-02 hepatocytes. In summary, EPC alleviated HFD-induced MAFLD by regulating lipid homeostasis and BA metabolism via the FXR/PPARα-SREBPs signaling pathway. P. cocos triterpenes, such as poricoic acid B and polyporenic acid C, were the characteristic substances of P. cocos for the treatment of MAFLD.
Coadministration of Compound Danshen dripping pills and bezafibrate has a protective effect against diabetic retinopathy
Authors: Liu Le , Li Xiaoqiang , Cai Wenbin , Guo Kaimin , Shi Xuelian , Tan Lu , Zhan Yao , Jing Xueshuang , Wang Wenjia , Zhou Shuiping , Sun He , Zhang Xu , Hu Yunhui
Published: October 2022

Diabetic retinopathy (DR) is increasingly becoming a main complication of diabetes, and is difficult to cure. In our research, network pharmacology analysis suggested that both compound Danshen dripping pills (CDDP) and bezafibrate (BZF) have potential protective effects against DR and the two drugs may act synergistically. The pharmacological effects of the coadministration of CDDP and BZF were elucidated in db/db mice, which simulate DR. Fluorescein fundus angiography showed that coadministration attenuated vascular leakage. Optical coherence tomography and hematoxylin and eosin staining showed that coadministration improved retinal thickness better than CDDP monotherapy. In addition, cell fluorescence images of reactive oxygen species revealed that coadministration of CDDP and BZF had more potent effects against oxidative stress than CDDP monotherapy. Metabolomics analysis showed that coadministration reduced the ratio of oxidized glutathione to reduced glutathione further than CDDP monotherapy. Coadministration of CDDP and BZF may provide additional protective effects by resisting vascular leakage, increasing retinal thickness, and inhibiting inflammation and oxidative stress in DR.
The pharmacological evidence of the chang-yan-ning formula in the treatment of colitis
Authors: Yu Wei , Zhang Yijia , Kang Cai , Zheng Yang , Liu Xincheng , Liang Zhenghao , Yan Jing
Published: October 2022

Ulcerative colitis (UC) is a subtype of inflammatory bowel disease (IBD) and occurs mainly in the colon. The etiology of UC is rather complex and involves various pathological factors, including genetic susceptibility, dietary intakes, environment, and microbiota. In China, the Chang-Yan-Ning (CYN) formula has been utilized in the clinic to treat gastrointestinal disorders, but its pharmacological evidence remains elusive. The investigation was designed to explore the molecular and cellular mechanisms of CYN. Liquid Chromatography with tandem mass spectrometry (LC/MS) was performed to identify the key components in the formula; Network pharmacology analysis was executed to predict the potential targets of CYN; An experimental murine colitis model was established by utilizing 2% dextran sodium sulfate (DSS), and CYN was administered for 14 days. The pharmacological mechanism of the CYN formula was corroborated by in-vivo and in-vitro experiments, and high throughput techniques including metabolomics and 16S rRNA sequencing. Results: LC/MS identified the active components in the formula, and network pharmacology analysis predicted 37 hub genes that were involved in tumor necrosis factor (TNF), interleukin (IL)-17, hypoxia-inducible factor (HIF) signaling pathways. As evidenced by in-vivo experiments, DSS administration shortened the length of the colon and led to weight loss, with a compromised structure of epithelium, and the CYN formula reversed these pathological symptoms. Moreover, CYN suppressed the levels of pro-inflammatory cytokines, including IL-4, IL-1b, and TNFαin the serum, inhibited the protein abundance of IL17 and HIF-1αand increased PPARγ and CCL2 in the colon, and facilitated the alternative activation of peritoneal macrophages. While peritoneal macrophages of colitis mice enhanced reactive oxygen species (ROS) production in murine intestinal organoids, the ROS level remained stable co-cultured with the macrophages of CYN-treated mice. Furthermore, the decreased microbiota richness and diversity and the prevalence of pathogenic taxa in colitis mice were rescued after the CYN treatment. The altered metabolic profile during colitis was also restored after the therapy. We posit that the CYN therapy attenuates the development and progression of colitis by maintaining the homeostasis of immune responses and microbiota.
Update on the recent development of allosteric modulators for adenosine receptors and their therapeutic applications
Authors: Pasquini Silvia , Contri Chiara , Cappello Martina , Borea Pier Andrea , Varani Katia , Vincenzi Fabrizio
Published: October 2022

Adenosine receptors (ARs) have been identified as promising therapeutic targets for countless pathological conditions, spanning from inflammatory diseases to central nervous system disorders, from cancer to metabolic diseases, from cardiovascular pathologies to respiratory diseases, and beyond. This extraordinary therapeutic potential is mainly due to the plurality of pathophysiological actions of adenosine and the ubiquitous expression of its receptors. This is, however, a double-edged sword that makes the clinical development of effective ligands with tolerable side effects difficult. Evidence of this is the low number of AR agonists or antagonists that have reached the market. An alternative approach is to target allosteric sites via allosteric modulators, compounds endowed with several advantages over orthosteric ligands. In addition to the typical advantages of allosteric modulators, those acting on ARs could benefit from the fact that adenosine levels are elevated in pathological tissues, thus potentially having negligible effects on normal tissues where adenosine levels are maintained low. Several A1 and various A3AR allosteric modulators have been identified so far, and some of them have been validated in different preclinical settings, achieving promising results. Less fruitful, instead, has been the discovery of A2A and A2BAR allosteric modulators, although the results obtained up to now are encouraging. Collectively, data in the literature suggests that allosteric modulators of ARs could represent valuable pharmacological tools, potentially able to overcome the limitations of orthosteric ligands.
The impacts of vitamin D supplementation in adults with metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials
Authors: Qi Kai-Jie , Zhao Zhong-Tao , Zhang Wen , Yang Fang
Published: October 2022

Background: Studies have shown the association of vitamin D status with the development of metabolic syndrome (MetS), which has attracted an extensive research interest with inconsistent results. Therefore, we hypothesized that vitamin D supplementation (VDS) will benefit adults with MetS.

Aims: To test our hypothesis, we performed a meta-analysis to evaluate the effect of VDS on MetS in adults using relevant biomarkers such as anthropometric parameters, blood pressure, blood lipid profile, glycemia, oxidative stress and vitamin D toxicity (VDT).

Methods: Randomized controlled trials published in PubMed, Web of Science, embase and the Cochrane Library between 2012 and 2022 on the effect of VDS on MetS in adults were searched. The language was limited to English. A meta-analysis performed using RevMan 5.4 and Stata 14.0 software, sensitivity analysis, and evaluation of the risk of bias and general quality of the resulting evidence were conducted.

Results: Eventually, 13 articles were included in this meta-analysis. Overall, VDS significantly increased the endline serum 25-hydroxyvitamin D levels as compared to the control [MD:17.41, 95% CI (14.09, 20.73), p < 0.00001]. VDS did not affect waist circumference, body mass index, body fat percentage and VDT biomarkers, but decreased waist-to-hip ratio and blood pressure (p < 0.01). VDS significantly decreased fasting plasma glucose (FPG) [MD: 3.78; 95% CI (−6.52, −1.03), p = 0.007], but did not affect the levels of blood high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG). Pooled estimate of nine papers indicated a significant reduction of fasting insulin (FI) (p = 0.006), and homeostasis model assessment of insulin resistance (p = 0.0001). The quantitative insulin check index levels were moderately increased (p = 0.007) without any impact on the glycosylated hemoglobin type A1C (HbA1c). For the oxidative stress parameters, VDS significantly lowered the levels of malondialdehyde and hypersensitive C-reactive protein (p < 0.05).

Conclusion: Results of this meta-analysis demonstrate that VDS only reduces insulin resistance and hypertension but not the blood lipid profile and HbA1c. It appears that the evidence for the benefit of VDS in adults with MetS is inconclusive. Further clinical studies are still needed.
Chinese herbal prescriptions for COVID-19 management: Special reference to Taiwan Chingguan Yihau (NRICM101)
Authors: Su Yi-Chang , Huang Guan-Jhong , Lin Jaung-Geng
Published: October 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. As at June 2022, increasing numbers of newly diagnosed COVID-19-associated pneumonia cases worldwide have attracted close attention from the international community. The present review analyzes and summarizes the treatment of COVID-19 with traditional Chinese medicine (TCM). A systematic analysis of the efficacies and benefits of TCM for the treatment of COVID-19 was performed, and the mechanisms underlying such treatment are summarized. This analysis of the literature highlights the potential of TCM to prevent and treat COVID-19 via antiviral, anti-inflammatory and immunomodulatory activities, with evidence showing that many TCM components act upon multiple targets and pathways. Famous TCM formulas include Qing-Fei-Pai-Du-Tang (QFPDT), Lianhuaqingwen Capsule (LHC), Taiwan Chingguan Yihau (NRICM101), and Jing Si herbal drink (JSHD). In particular, the botanical preparation NRICM101 was developed in 2020 for use in viral respiratory tract infections and is recommended for treating non-severe and mild COVID-19 infections. NRICM101 has been adopted for use in Taiwan for the clinical treatment of COVID-19. The common components and active ingredients of 10 TCM preparations have been analyzed for the most promising substances. This review aims to provide reliable evidence demonstrating the therapeutic efficacy of TCM substances in support of their further development against novel coronavirus infectious diseases in Taiwan.
Improving the efficacy for meropenem therapy requires a high probability of target attainment in critically ill infants and children
Authors: Wang Zeming , Bi Jing , You Dianping , Tang Yu , Liu Gang , Yu Jinqian , Jin Zhipeng , Jiang Tingting , Tian Xue , Qi Hui , Dong Lei , Dong Lili , Zhang Qunqun , Zhao Wei , Shen Adong
Published: October 2022

Probability of target attainment is the key factor influencing the outcome of meropenem therapy. The objective of the present study was to evaluate the relationship between the time in which the plasma free concentration of meropenem exceeds the minimum inhibitory concentration of pathogens (fT>MIC) during therapy and the clinical outcome of treatment to optimize meropenem therapy. Critically ill children with infections who had received intravenous meropenem monotherapy were included. The relationship between fT>MIC of meropenem and effectiveness and safety were explored. Data from 53 children (mean age ± standard deviation, 26 months ± 38) were available for final analysis. Children with fT>MIC ≥ 5.6 h (n = 14) had a more significant improvement in antibacterial efficacy in terms of decrease in fever (p = 0.02), white blood cell count (p = 0.014), and C-reactive protein (p = 0.02) compared with children with fT>MIC < 5.6 h (n = 39) after meropenem therapy completed. No drug-related adverse events were shown to have a causal association with meropenem therapy. Our study shows the clinical benefits of sufficient target attainment of meropenem therapy. Meeting a suitable pharmacodynamic target attainment of meropenem is required to ensure better antibacterial efficacy in critically ill infants and children.

Clinical Trial Registration:clinicaltrials.gov, Identifier NCT03643497.
Herbal therapies in gastrointestinal and hepatic disorders: An evidence-based clinical review
Authors: Yao Yongfang , Habib Murad , Bajwa Hajra Fazeelat , Qureshi Anina , Fareed Rameesha , Altaf Reem , Ilyas Umair , Duan Yongtao , Abbas Muhammad
Published: October 2022

The gastrointestinal tract (GIT) and the liver constitute the major organs of the human body. Indeed, the very survival of the human body depends on their proper functioning. Because the GIT is a huge and complex organ system, the maintenance of proper GIT and liver health is an arduous task. GIT disturbances such as diarrhea, stomach ache, flatulence, constipation, nausea, and vomiting are very common, and they contribute to a significant burden on the healthcare system. Pharmacies are full of over-the-counter pharmacological drugs to alleviate its common conditions. However, these drugs do not always prove to be fully effective and patients have to keep on living with these ailments without a proper and long-term solution. The aim of this review article is to present a practical reference guide to the role of herbal medicines in dealing with gastrointestinal and hepatic disorders, which is supported by systematic reviews and evidence-based trials. People have depended on herbal medications for centuries for the treatment of various ailments of the GIT, liver, and other organ system problems. Recently, this trend of incorporating herbal medication for the treatment of various diseases in both developing and developed countries have surged. Many people continue to use herbal medications, even though substantial data about their efficacy, uses, and toxicological effects do not exist. In addition, while herbal medicines have enormous benefits in both the prevention and the treatment of medical ailments, they can also have toxicological effects. It is, therefore, of the utmost importance that appropriate time, energy, and resources are spent on the development of ethnopharmacology. In addition, herbal products should be classified in a pattern similar to pharmacological medications, including their uses, side effects, mechanism of action, efficacy, and so on.
Screening of potential inhibitors targeting the main protease structure of SARS-CoV-2 via molecular docking
Authors: Yang Xinbo , Xing Xianrong , Liu Yirui , Zheng Yuanjie
Published: October 2022

The novel coronavirus disease (COVID-19) caused by SARS-CoV-2 virus spreads rapidly to become a global pandemic. Researchers have been working to develop specific drugs to treat COVID-19. The main protease (Mpro) of SARS-CoV-2 virus plays a pivotal role in mediating viral replication and transcription, which makes it a potential therapeutic drug target against COVID-19. In this study, a virtual drug screening method based on the Mpro structure (Protein Data Bank ID: 6LU7) was proposed, and 8,820 compounds collected from the DrugBank database were used for molecular docking and virtual screening. A data set containing 1,545 drug molecules, derived from compounds with a low binding free energy score in the docking experiment, was established. N-1H-Indazol-5-yl-2-(6-methylpyridin-2-yl)quinazolin-4-amine, ergotamine, antrafenine, dihydroergotamine, and phthalocyanine outperformed the other compounds in binding conformation and binding free energy over the N3 inhibitor in the crystal structure. The bioactivity and ADMET properties of these five compounds were further investigated. These experimental results for five compounds suggested that they were potential therapeutics to be developed for clinical trials. To further verify the results of molecular docking, we also carried out molecular dynamics (MD) simulations on the complexes formed by the five compounds and Mpro. The five complexes showed stable affinity in terms of root mean square distance (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and hydrogen bond. It was further confirmed that the five compounds had potential inhibitory effects on SARS-CoV-2 Mpro.
A meta-analysis of resveratrol protects against cerebral ischemia/reperfusion injury: Evidence from rats studies and insight into molecular mechanisms
Authors: Xue Ruirui , Gao Shuang , Zhang Yayun , Cui Xuejun , Mo Wen , Xu Jinhai , Yao Min
Published: October 2022

Objective: To evaluate the neuroprotective effect of resveratrol (RES) in rat models of cerebral ischemia/reperfusion (I/R) injury.

Data sources: PubMed, Embase, MEDLINE, Cochrane Library, and Chinese databases were searched from their inception dates to July 2022. No language restriction was used in the literature search.

Date Selection: Studies were selected that RES were used to treat cerebral I/R injury in vivo. Two reviewers conducted literature screening, data extraction and methodological quality assessment independently.

Outcome measures: Cerebral infarct volume was included as primary outcome. The secondary outcomes included cerebral water content and neurological deficit scores. Malondialdehyde (MDA) and superoxide dismutase (SOD) were used to evaluate oxidative stress during medication.

Results: A total of 41 studies were included, and only a few of them the methodological quality was relatively low. Compared with the control group, RES significantly reduced the cerebral infarct volume (29 studies, standard mean difference (SMD) = −2.88 [−3.23 to −2.53], p < 0.00001) and brain water content (nine studies, MD = −9.49 [−13.58 to −5.40], p < 0.00001) after cerebral I/R injury, then neurological function was improved (15 studies, SMD = −1.96 [−2.26 to −1.65], p < 0.00001). The MDA level (six studies, SMD = −8.97 [−13.60 to −4.34], p = 0.0001) was decreased notably after treatment of RES, while the SOD level (five studies, SMD = 3.13 [−0.16 to 6.43], p = 0.06) was increased unsatisfactory. Consistently, subgroup analysis of cerebral infarct volume suggested that the optimal therapeutic dose is 30 mg/kg (eight studies, SMD = −5.83 [−7.63 to −4.04], p < 0.00001). Meanwhile, 60 min of occlusion (three studies, SMD = −10.89 [−16.35 to −5.42], p < 0.0001) could get maximum benefit from compared with 90 min and 120 min of occlusion. On the other hand, the publication bias cannot be ignored. The pharmacological mechanisms of RES on cerebral I/R injury models as reported have be summarized, which can be used for reference by researchers to further plan their future experiments.

Conclusion: RES might have a good neuroprotective effect on cerebral I/R injury in rats, then 30 mg/kg RES may be the optimal dose for treatment, and early administration of RES should be more neuroprotective. Also it need to be further verified through exploration of dose effect relationship, or delay administration or not.
Protective effect of zinc oxide nanoparticles on spinal cord injury
Authors: Liu Jia , Huang Zhendong , Yin Suhan , Jiang Yanping , Shao Longquan
Published: October 2022

The microenvironmental changes in the lesion area of spinal cord injury (SCI) have been extensively studied, but little is known about the whole-body status after injury. We analyzed the peripheral blood RNA-seq samples from 38 SCI and 10 healthy controls, and identified 10 key differentially expressed genes in peripheral blood of patients with SCI. Using these key gene signatures, we constructed a precise and available neural network diagnostic model. More importantly, the altered transcriptome profiles in peripheral blood reflect the similar negative effects after neuronal damage at lesion site. We revealed significant differential alterations in immune and metabolic processes, therein, immune response, oxidative stress, mitochondrial metabolism and cellular apoptosis after SCI were the main features. Natural agents have now been considered as promising candidates to alleviate/cure neuronal damage. In this study, we constructed an in vitro neuronal axotomy model to investigate the therapeutic effects of zinc oxide nanoparticles (ZnO NPs). We found that ZnO NPs could act as a neuroprotective agent to reduce oxidative stress levels and finally rescue the neuronal apoptosis after axotomy, where the PI3K-Akt signaling probably be a vital pathway. In conclusion, this study showed altered transcriptome of peripheral blood after SCI, and indicated the neuroprotective effect of ZnO NPs from perspective of oxidative stress, these results may provide new insights for SCI diagnosis and therapeutics.
The incidence of opportunistic infections in patients with psoriatic arthritis treated with biologic and targeted synthetic agents: A systematic review and meta-analysis
Authors: Vassilopoulos Athanasios , Shehadeh Fadi , Benitez Gregorio , Kalligeros Markos , Cunha Joanne S. , Cunha Cheston B. , Mylonakis Eleftherios
Published: October 2022

Background: Biologic (bDMARD) and targeted synthetic (tsDMARD) disease-modifying anti-rheumatic drugs have broadened the treatment options and are increasingly used for patients with psoriatic arthritis (PsA). These agents block different pro-inflammatory cytokines or specific intracellular signaling pathways that promote inflammation and can place patients at risk of serious infections. We aimed to review the incidence of opportunistic infections (OIs) in patients with PsA who were treated with these agents.

Methods: We searched PubMed and EMBASE through 14 April 2022 for randomized clinical trials evaluating bDMARD or tsDMARD in the treatment of PsA. Trials were eligible if they compared the effect of a bDMARD or tsDMARD with placebo and provided safety data. We used the Revised Cochrane risk-of-bias tool to assess the risk of bias among trials, and stratified the studies by mechanism of action (MOA) of the agents studied.

Results: We included 47 studies in this analysis. A total of 17,197 patients received at least one dose of an agent of interest. The cumulative incidence of OIs by MOA was as follows: 1) JAK inhibitors: 2.72% (95% CI: 1.05%–5.04%), 2) anti-IL-17: 1.18% (95% CI: 0.60%–1.9%), 3) anti-IL-23: 0.24% (95% CI: 0.04%–0.54%), and 4) anti-TNFs: 0.01% (95% CI: 0.00%–0.21%). Based on their MOA, these agents are known to increase the risk of certain serious infections. The cumulative incidence of herpes zoster infection following treatment with JAK inhibitors (JAKi) was 2.53% (95% CI: 1.03%–4.57%) and the cumulative incidence of opportunistic Candida spp. infections following treatment with anti-IL-17, was 0.97% (95% CI: 0.51%–1.56%).

Conclusion: The overall incidence of OIs among patients with PsA who were treated with biologic and targeted synthetic agents is low. However, careful monitoring is warranted for specific OIs such as herpes zoster infection following JAKi treatment, mucocutaneous candidiasis following anti-IL-17 treatment, and Mycobacterium tuberculosis infection following anti-TNF treatment.
Resonant two-photon ionization of helium atoms studied by attosecond interferometry
Authors: Neoričić L. , Busto D. , Laurell H. , Weissenbilder R. , Ammitzböll M. , Luo S. , Peschel J. , Wikmark H. , Lahl J. , Maclot S. , Squibb R. J. , Zhong S. , Eng-Johnsson P. , Arnold C. L. , Feifel R. , Gisselbrecht M. , Lindroth E. , L’Huillier A.
Published: October 2022

We study resonant two-photon ionization of helium atoms via the 1s3p, 1s4p and 1s5p1P1 states using the 15th harmonic of a titanium-sapphire laser for the excitation and a weak fraction of the laser field for the ionization. The phase of the photoelectron wavepackets is measured by an attosecond interferometric technique, using the 17th harmonic. We perform experiments with angular resolution using a velocity map imaging spectrometer and with high energy resolution using a magnetic bottle electron spectrometer. Our results are compared to calculations using the two-photon random phase approximation with exchange to account for electron correlation effects. We give an interpretation for the multiple π-rad phase jumps observed, both at and away from resonance, as well as their dependence on the emission angle.
Teleostean fishes may have developed an efficient Na+ uptake for adaptation to the freshwater system
Authors: Tseng Yung-Che , Yan Jia-Jiun , Furukawa Fumiya , Chen Ruo-Dong , Lee Jay-Ron , Tsou Yi-Ling , Liu Tzu-Yen , Tang Yu-Hsin , Hwang Pung-Pung
Published: October 2022

Understanding Na+ uptake mechanisms in vertebrates has been a research priority since vertebrate ancestors were thought to originate from hyperosmotic marine habitats to the hypoosmotic freshwater system. Given the evolutionary success of osmoregulator teleosts, these freshwater conquerors from the marine habitats are reasonably considered to develop the traits of absorbing Na+ from the Na+-poor circumstances for ionic homeostasis. However, in teleosts, the loss of epithelial Na+ channel (ENaC) has long been a mystery and an issue under debate in the evolution of vertebrates. In this study, we evaluate the idea that energetic efficiency in teleosts may have been improved by selection for ENaC loss and an evolved energy-saving alternative, the Na+/H+ exchangers (NHE3)-mediated Na+ uptake/NH4+ excretion machinery. The present study approaches this question from the lamprey, a pioneer invader of freshwater habitats, initially developed ENaC-mediated Na+ uptake driven by energy-consuming apical H+-ATPase (VHA) in the gills, similar to amphibian skin and external gills. Later, teleosts may have intensified ammonotelism to generate larger NH4+ outward gradients that facilitate NHE3-mediated Na+ uptake against an unfavorable Na+ gradient in freshwater without consuming additional ATP. Therefore, this study provides a fresh starting point for expanding our understanding of vertebrate ion regulation and environmental adaptation within the framework of the energy constraint concept.
Airway smooth muscle function in asthma
Authors: Xiong Dora (Jun Ping) , Martin James G. , Lauzon Anne-Marie
Published: October 2022

Known to have affected around 340 million people across the world in 2018, asthma is a prevalent chronic inflammatory disease of the airways. The symptoms such as wheezing, dyspnea, chest tightness, and cough reflect episodes of reversible airway obstruction. Asthma is a heterogeneous disease that varies in clinical presentation, severity, and pathobiology, but consistently features airway hyperresponsiveness (AHR)—excessive airway narrowing due to an exaggerated response of the airways to various stimuli. Airway smooth muscle (ASM) is the major effector of exaggerated airway narrowing and AHR and many factors may contribute to its altered function in asthma. These include genetic predispositions, early life exposure to viruses, pollutants and allergens that lead to chronic exposure to inflammatory cells and mediators, altered innervation, airway structural cell remodeling, and airway mechanical stress. Early studies aiming to address the dysfunctional nature of ASM in the etiology and pathogenesis of asthma have been inconclusive due to the methodological limitations in assessing the intrapulmonary airways, the site of asthma. The study of the trachealis, although convenient, has been misleading as it has shown no alterations in asthma and it is not as exposed to inflammatory cells as intrapulmonary ASM. Furthermore, the cartilage rings offer protection against stress and strain of repeated contractions. More recent strategies that allow for the isolation of viable intrapulmonary ASM tissue reveal significant mechanical differences between asthmatic and non-asthmatic tissues. This review will thus summarize the latest techniques used to study ASM mechanics within its environment and in isolation, identify the potential causes of the discrepancy between the ASM of the extra- and intrapulmonary airways, and address future directions that may lead to an improved understanding of ASM hypercontractility in asthma.
CAN OF SPINACH, a novel long non-coding RNA, affects iron deficiency responses in Arabidopsis thaliana
Authors: Bakirbas Ahmet , Walker Elsbeth L.
Published: October 2022

Long non-coding RNAs (lncRNAs) are RNA molecules with functions independent of any protein-coding potential. A whole transcriptome (RNA-seq) study of Arabidopsis shoots under iron sufficient and deficient conditions was carried out to determine the genes that are iron-regulated in the shoots. We identified two previously unannotated transcripts on chromosome 1 that are significantly iron-regulated. We have called this iron-regulated lncRNA, CAN OF SPINACH (COS). cos mutants have altered iron levels in leaves and seeds. Despite the low iron levels in the leaves, cos mutants have higher chlorophyll levels than WT plants. Moreover, cos mutants have abnormal development during iron deficiency. Roots of cos mutants are longer than those of WT plants, when grown on iron deficient medium. In addition, cos mutant plants accumulate singlet oxygen during iron deficiency. The mechanism through which COS affects iron deficiency responses is unclear, but small regions of sequence similarity to several genes involved in iron deficiency responses occur in COS, and small RNAs from these regions have been detected. We hypothesize that COS is required for normal adaptation to iron deficiency conditions.
Comparative chloroplast genome analyses of Paraboea (Gesneriaceae): Insights into adaptive evolution and phylogenetic analysis
Authors: Wang Yifei , Wen Fang , Hong Xin , Li Zhenglong , Mi Yaolei , Zhao Bo
Published: October 2022

Paraboea (Gesneriaceae) distributed in the karst areas of South and Southwest China and Southeast Asia, is an ideal genus to study the phylogeny and adaptive evolution of karst plants. In this study, the complete chloroplast genomes of twelve Paraboea species were sequenced and analyzed. Twelve chloroplast genomes ranged in size from 153166 to 154245 bp. Each chloroplast genome had a typical quartile structure, and relatively conserved type and number of gene components, including 131 genes which are composed of 87 protein coding genes, 36 transfer RNAs and 8 ribosomal RNAs. A total of 600 simple sequence repeats and 389 non-overlapped sequence repeats were obtained from the twelve Paraboea chloroplast genomes. We found ten divergent regions (trnH-GUG-psbA, trnM-CAU, trnC-GCA, atpF-atpH, ycf1, trnK-UUU-rps16, rps15, petL, trnS-GCU-trnR-UCU and psaJ-rpl33) among the 12 Paraboea species to be potential molecular markers. In the phylogenetic tree of 31 Gesneriaceae plants including twelve Paraboea species, all Paraboea species clustered in a clade and confirmed the monophyly of Paraboea. Nine genes with positive selection sites were detected, most of which were related to photosynthesis and protein synthesis, and might played crucial roles in the adaptability of Paraboea to diverse karst environments. These findings are valuable for further study of the phylogeny and karst adaptability of Gesneriaceae plants.
Sulfur reduces the root-to-shoot translocation of arsenic and cadmium by regulating their vacuolar sequestration in wheat (Triticum aestivum L.)
Authors: Shi Gaoling , Liu Huan , Zhou Dongmei , Zhou Huimin , Fan Guangping , Chen Wei , Li Jiangye , Lou Laiqing , Gao Yan
Published: October 2022

Accumulation of arsenic (As) and cadmium (Cd) in wheat grain is a serious threat to human health. Sulfur (S) can simultaneously decrease wheat grain As and Cd concentrations by decreasing their translocation in wheat; however, the mechanisms are unclear. We conducted hydroponic experiments to explore the mechanisms by which S modulates As and Cd translocation and their toxicity in wheat. Wheat seedlings were grown in deficient sulfate (2.5 µM) or sufficient sulfate (1.0 mM) nutrient solutions for 6 days and then exposed to zero (control), low As+Cd (1 µM As plus 0.5 µM Cd), or high As+Cd (50 µM As plus 30 µM Cd) for another 6 days. Compared with the control, plant growth was not affected by low As+Cd, but was significantly inhibited by high As+Cd. In the low As+Cd treatment, S supply had no significant effect on plant growth or root-to-shoot As and Cd translocation. In the high As+Cd treatment, sufficient S supply significantly alleviated As and Cd toxicity and their translocation by increasing phytochelatin (PC) synthesis and the subsequent vacuolar sequestration of As and Cd in roots, compared with deficient S supply. The use of L-buthionine sulfoximine (a specific inhibitor of γ-glutamylcysteine synthetase) confirmed that the alleviation of As and Cd translocation and toxicity in wheat by S is mediated by increased PC production. Also, TaHMA3 gene expression in wheat root was not affected by the As+Cd and S treatments, but the expression of TaABCC1 was upregulated by the high As+Cd treatment and further increased by sufficient S supply and high As+Cd treatment. These results indicate that S-induced As and Cd subcellular changes affect As and Cd translocation mainly by regulating thiol metabolism and ABCC1 expression in wheat under As and Cd stress.
Molecular mechanisms of resistance to Myzus persicae conferred by the peach Rm2 gene: A multi-omics view
Authors: Le Boulch Pauline , Poëssel Jean-Luc , Roux David , Lugan Raphaël
Published: October 2022

The transcriptomic and metabolomic responses of peach to Myzus persicae infestation were studied in Rubira, an accession carrying the major resistance gene Rm2 causing antixenosis, and GF305, a susceptible accession. Transcriptome and metabolome showed both a massive reconfiguration in Rubira 48 hours after infestation while GF305 displayed very limited changes. The Rubira immune system was massively stimulated, with simultaneous activation of genes encoding cell surface receptors involved in pattern-triggered immunity and cytoplasmic NLRs (nucleotide-binding domain, leucine-rich repeat containing proteins) involved in effector-triggered immunity. Hypersensitive reaction featured by necrotic lesions surrounding stylet punctures was supported by the induction of cell death stimulating NLRs/helpers couples, as well as the activation of H2O2-generating metabolic pathways: photorespiratory glyoxylate synthesis and activation of the futile P5C/proline cycle. The triggering of systemic acquired resistance was suggested by the activation of pipecolate pathway and accumulation of this defense hormone together with salicylate. Important reduction in carbon, nitrogen and sulphur metabolic pools and the repression of many genes related to cell division and growth, consistent with reduced apices elongation, suggested a decline in the nutritional value of apices. Finally, the accumulation of caffeic acid conjugates pointed toward their contribution as deterrent and/or toxic compounds in the mechanisms of resistance.
COVID-19 alters the relationship between relational mobility and helping behavior
Authors: Zhang Xiaoxiao , Zhao Xian , Liao Gengnan , Huang Yuanlin , Fang Xuan
Published: October 2022

To determine if helping behaviors are affected by socioecological variables such as relational mobility and the COVID-19 pandemic, we investigated the impact of relational mobility on helping behaviors before (Study 1) and during (Study 2) COVID-19 in China via two experiments. In Study 1, we manipulated participants’ relational mobility and found that a greater proportion of participants in the high relational mobility condition signed up for another psychological experiment, relative to the low relational mobility condition. In Study 2, the manipulation of relational mobility was embedded in a phone interview, and we found that a high relational mobility condition caused fewer signups for a COVID-19 support program relative to a low relational mobility condition. These results extend our understanding of the meaning of relational mobility under different ecological contexts.
Negotiating the impact of international experiences on professional identity development: A case study of Chinese college English teachers
Authors: Zhang Fengjuan , Wang Jing
Published: October 2022

This study traced changes in Chinese college English teachers’ professional identities as a result of participating in international professional development programs and examined how the teachers negotiated their professional identities upon return to China. Five college English teachers with at least 10 months of overseas professional development experience took part in the study. Data were collected through semi-structured interviews and relevant documents. It was found that international experiences had a great impact on the teachers’ professional identity construction by empowering them to develop multiple identities as language teaching professionals, university academics, and change agents. The teachers’ reconstruction of professional identities upon return to China was not a linear and smooth process. It was a dynamic process of negotiating with the constraints of the personal and professional contexts to which the teachers returned. The study sheds light on the identity development of internationally trained language teachers and contributes to a deeper understanding of the impact of international experiences on the professional development of second language teachers in similar contexts. It has implications for study abroad programs and for home institutions about how to support the long-term professional development of returnee teachers.
Travel despite the COVID-19 pandemic: Implications for tourism recovery
Authors: Liu Hongbo , Liu-Lastres Bingjie , Zeng Li , Donohoe Holly
Published: October 2022

The COVID-19 pandemic has devastated the global tourism industry. This study explores why some Chinese residents travel during the pandemic. A mixed-methods research design was adopted, guided by the health belief model and relevant literature. Through 21 interviews with Chinese tourists who took an overnight leisure trip in May 2020, and a national survey among Chinese residents, this study explored factors influencing Chinese residents’ travel-related decisions and behaviors during the pandemic. Results outline the influences of health beliefs, government trust, past travel experience, and psychological capital on tourists’ risk-reduction behaviors. Theoretical and practical implications are provided regarding tourism recovery during pandemics.
Effects of exercise and psychological interventions on smartphone addiction among university students: A systematic review
Authors: Liu Huange , Soh Kim Geok , Samsudin Shamsulariffin , Rattanakoses Watnawat , Qi Fengmeng
Published: October 2022

Background and aims

Among the large number of studies on smartphone addiction, only a few randomized controlled trials on exercise and psychological interventions for smartphone addiction by university students have been published. This study aims to systematically investigate the impact of exercise and psychological interventions on smartphone addiction among university students.

Methods

The PRISMA guidelines were adopted for this systematic literature review. Prominent academic databases such as Web of Science, PubMed, ProQuest, Cochrane Library, China National Knowledge Infrastructure (CNKI) and PsycINFO were searched to find eligible studies published before Aug 2021. The overall quality of the articles was checked using the “QualSyst” tool by Kmet et al.

Results

From among 600 papers, 23 met the inclusion criteria and were incorporated into our systematic review. All of the studies were randomized controlled trials. The following thematic areas emerged as a result of the content analysis: study selection and design, as well as study characteristics (participants, intervention, comparisons, and outcomes).

Discussion and conclusion

The literature on exercise and psychological interventions for smartphone addiction is scarce. There is a need to introduce new interventions and to validate the effectiveness of combined interventions. Our findings suggest that exercise and psychological interventions may help to reduce smartphone addiction. This combination was more effective compare to exercise or psychological intervention on mental health and addiction among university students. Future research should combine exercise and psychological interventions, focusing on university students, especially females, who are vulnerable to smartphone addiction. Further studies should focus on the cross-section of neuropsychology, cognitive psychology, and sports science to provide combined interventions in physiological and psychological direction.

Systematic review registration

https://www.crd.york.ac.uk/prospero, identifier: CRD42021278037.
Green credit and enterprise green operation: Based on the perspective of enterprise green transformation
Authors: Niu Haiyan , Zhao Xiongfei , Luo Zhilin , Gong Yuxia , Zhang Xinhua
Published: October 2022

This paper uses panel data of listed heavily polluting enterprises from 2007 to 2021, based on the perspective of transformation and upgrading of heavy polluters, innovatively studies the impact of green credit on the green operation of enterprises. At the micro level, the research results of this paper verify the effectiveness of green credit policy on the transformation of green enterprises. It is also found that the two intermediary paths of debt cost and government subsidy play a partial intermediary role in the process of green credit promoting green enterprise transformation and upgrading. Green credit policy also moderates the green transformation of enterprises through debt cost and government subsidies. Based on the research results, this paper puts forward targeted policy suggestions from the aspects of financing constraints, government subsidy policies, enterprise technological innovation and green operation, and provides empirical support for the current expansion of green credit policies in China.