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BackgroundRegulatory T cells (Tregs) have been found to play crucial roles in immune tolerance. However, the status of Tregs in refractory rheumatoid arthritis (RA) is still unclear. Moreover, low-dose interleukin-2 (IL-2) has been reported to selectively promote the expansion of Tregs. This study investigated the status of CD4+ Tregs and low-dose IL-2 therapy in patients with refractory RA.MethodsThe absolute number of CD4+CD25+FOXP3+ Treg (CD4 Treg), CD4+IL17+ T (Th17), and other subsets in peripheral blood (PB) from 41 patients with refractory RA and 40 healthy donors was characterized by flow cytometry combined with an internal microsphere counting standard. Twenty-six patients with refractory RA were treated with daily subcutaneous injections of 0.5 million IU of human IL-2 for five consecutive days. Then, its effects on CD4 Treg and Th17 cells in PB were analyzed.ResultsA decrease in the absolute number of PB CD4 Tregs rather than the increase in the number of Th17 was found to contribute to an imbalance between Th17 and CD4 Tregs in these patients, suggesting an essential role of CD4 Tregs in sustained high disease activity. Low-dose IL-2 selectively increased the number of CD4 Tregs and rebalanced the ratio of Th17 and CD4 Tregs, leading to increased clinical symptom remission without the observed side effects.ConclusionsAn absolute decrease of PB CD4 Tregs in patients with refractory RA was associated with continuing disease activation but not the increase of Th17 cells. Low-dose IL-2, a potential therapeutic candidate, restored decreased CD4 Tregs and promoted the rapid remission of patients with refractory RA without overtreatment and the observed side effects.Clinical trial registrationhttp://www.chictr.org.cn/showproj.aspx?proj=13909, identifier ChiCTR-INR-16009546.

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The shortage of water resources is a long-standing constraint on the development of the Chinese economy and society. In this paper, the climate change occurring in Hulan River Basin is analyzed using the data collected at Wangkui Meteorological Station from 1960 to 2020. The overall temperature in the basin shows an upward trend, with a cumulative increase of 1.6 °C, as does the precipitation, which reaches 566.2 mm. In contrast, there is a downward trend shown by wind speed, with a cumulative decrease of 1.313 m/s. GIS remote sensing technology is applied to build a SWAT distributed hydrological model for the purpose of conducting runoff simulation in Hulan River Basin, and SWAT-CUP software is used to correct and analyze the simulation results. The parameters of snow melt are set to improve the accuracy of the model. The runoff data collected from Lanxi Hydrological Station from 2008 to 2020 are used to verify the model. The results show that the efficiency coefficient (NES) and correlation coefficient (R2) are 0.75 and 0.84, respectively, in the validation period from 2010 to 2013, while they are 0.77 and 0.93, respectively, in the correction period from 2014 to 2016, meeting the criteria of model evaluation. It can be seen from results noted above that SWAT is applicable in Hulan River Basin, providing a certain reference for the management of hydrological and water resources available in this region and for the construction of a distributed hydrological model of rivers in those high-latitude cold regions.

The best time window of percutaneous coronary intervention (PCI) is within 12 hours for ST-segment elevation myocardial infarction (STEMI). However, there is limited evidence about the proper time of PCI for delayed STEMI patients.From June 2014 to June 2015, a total of 268 patients receiving PCI with second-generation drug-eluting stent in a Chinese hospital after 3 days of STEMI onset were enrolled in this retrospective study, who were divided into the early group (3-14 days) and the late group (>14 days). A propensity score match was conducted to reduce the baseline difference. The primary endpoint of all-cause death and secondary endpoints of major adverse cardiac and cerebrovascular event (myocardial infarction [MI], stroke, emergent revascularization, and rehospitalization due to heart failure) were compared using survival analysis.At last, 182 cases were matched after propensity score match, with no statistical difference in baseline characteristics and PCI data. Kaplan-Meier survival curve demonstrated no difference in all-cause death of the 2 groups (P = .512). However, the early group presented a higher incidence of MI than the late group (P = .036). The multivariate Cox regression analysis also demonstrated that the early PCI was an independent risk factor for MI compared with late PCI (hazard ratio = 3.83, ], P = .001). There was no statistical difference in other major adverse cardiac and cerebrovascular event, including stroke, emergent revascularization, and rehospitalization due to heart failure.Using the 2 nd drug-eluting stent, early PCI (3-14 days) and late PCI (>14 days) have comparable efficacy and outcomes. However, patients receiving early PCI are subjected to a relatively higher risk of recurrent MI.Abbreviations: CAD = coronary artery disease, DES = drug-eluting stent, HR = hazard ratio, MACCE = major adverse cardiac and cerebrovascular event, MI = myocardial infarction, PCI = percutaneous coronary intervention, PSM = propensity score match, STEMI = ST-segment elevation myocardial infarction.

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Background As one of the most critical proteins in the JAK/STAT signaling pathway, Janus kinase 2 (JAK2) is involved in many biological processes and diseases. Several observational studies have reported the role of JAK2 in erectile dysfunction. However, the causal relationship between JAK2 and erectile dysfunction remains unclear. Here we investigated the causal relationship between JAK2 and erectile dysfunction. Results Genetically predicted JAK2 was causally associated with erectile dysfunction in inverse variance weighting (OR = 1.109, 95% CI = 1.029–1.196, p = 0.007) and weighted median method (OR = 1.117, 95% CI = 1.003-1.245, p = 0.044). No heterogeneity was observed in Cochran Q-test (p = 0.855) and MR-PRESSO (p = 0.866). Pleiotropy was not observed in our study (p = 0.617). Conclusions These findings highlighted JAK2 as a risk factor for erectile dysfunction and proved the causal relationship between JAK2 and erectile dysfunction, suggesting that targeting JAK2 signaling might be a novel and promising therapeutic candidate in the treatment of erectile dysfunction.

BackgroundAnkylosing spondylitis (AS) is a common chronic inflammatory autoimmune disease that primarily affects the sacroiliac joints, spine and peripheral joints, and attachments of ligaments. Regulatory B cells (Bregs) are unique subpopulations of B cells with immune-regulating properties. Interestingly, different subsets of Breg cells have distinct markers and phenotypes and participate in self-immune regulation in different ways. However, the level of Breg cells in AS remains debated.ObjectivesThis study aims to clarify the proportions of Breg cells with unique, controversial cellular markers in AS patients.MethodsWe explored the proportion of Breg cells in AS patients by searching literature through January 10, 2023, from 11 Databases. Random effects model was used to pool data. Heterogeneity and risk of bias were examined with the I-squared index (I2) statistic. Inconsistency was evaluated using the I2and Egger tests to evaluate potential publication bias (STATA v.12.0).ResultsA total of 7 case-control studies involving 278 AS patients and 237 healthy controls (HCs) were included in this study(Table 1). No significant difference in the proportions of Breg cells was evident between AS patients and HCs[SMD=-0.324, 95%CI(-0.971, 0.323), P=0.327]. Because of a significant statistical heterogeneity observed [p<0.1, I2=89.2%], we conducted sub-analyses based on individual definitions of Breg cells. We found that the proportions of CD19+CD24hiCD38hiBreg cells have no significant difference between AS and HCs [SMD=-0.546, 95%CI (-1.126, 0.034), P=0.065](Figure 1). The level of CD19+CD24hiCD27+Breg cells was increased in AS compared to that of HCs[SMD=0.965, 95%CI (0.339, 1.590), P=0.003] with no publication bias based on the Egger tests (t=1.35, p=0.236).ConclusionThe levels of CD19+CD24hiCD27+Breg cells were significantly increased in AS patients, suggesting that the abnormalities of Breg cell numbers and function are the critical causes in the development of AS.Table 1.Characteristics of the individual studies included in the meta-analysis.AuthorPublishyearCase numberBreg cells’definitionBreg cell ratio (mean/ median±standard deviation)Breg in PBMC/CD19+B cellsASHCYu Zhang20224230CD19+CD24hiCD38hiAS:6.125±4.219 HC:9.021±4.527PBMCGuo-Hui Xue20153830CD19+CD24hiCD38hiAS:2.1±0.66 HC:3.44±0.8PBMCXiao-Wan Huang20141018CD19+CD24hiCD38hiAS:7.15±2.0277 HC:6.87748±1.9131PBMCMingcan Yang20206750CD19+CD24hiCD38hiAS:1.84812±2.1178 HC:2.03012±4.2419PBMCMaria-Belen Bautista-Caro120174242CD19+CD24hiCD38hiAS:3.412±1.011 HC:4.361±1.744PBMCZhangyu20204230CD19+CD24hiCD38hiAS:6.2±3.2 HC:8.6±4.0PBMCZhukangxiang20212222CD19+CD24hiCD27+AS:16.5±3.5 HC:13.4±2.9PBMCChenmeng20161515CD19+CD24hiCD38hiAS:9.8±1.1HC:9±1.4PBMCFigure 1.(A) Forest plot of the subgroup meta-analysis of individual definitions of peripheral Breg cell proportions between patients and HCs.AcknowledgementsThis work was supported by the National Natural Science Foundation of China (No. 82001740).Disclosure of InterestsNone Declared.