Objective To investigate the effects of hyaluronic acid and proteoglycan-linked protein 1 (HAPLN1) secreted by synovial fibroblasts (FLS) on the polarization of macrophages (Mϕ) in rheumatoid arthritis (RA). Methods Human monocytic leukemia cells (THP-1) were differentiated into Mϕ, which were subsequently exposed to recombinant HAPLN1 (rHAPLN1). RA-FLS were transfected separately with HAPLN1 overexpression plasmid (HAPLN1^OE) or small interfering RNA targeting HAPLN1 (si-HAPLN1), and then co-cultured with Mϕ to establish a co-culture model. The viability of Mϕ was assessed using the CCK-8 assay, and the proportions of pro-inflammatory M1-type and anti-inflammatory M2-type Mϕ were analyzed by flow cytometry. Additionally, the expression levels of inflammatory markers, including interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS), were quantified using quantitative real-time PCR and Western blot analysis. Results The viability of Mϕ was increased in the rHAPLN1 group compared to the control group. Furthermore, both the M1/Mϕ ratio and inflammatory factor levels were elevated in the rHAPLN1 and HAPLN1^OE groups. In contrast, the si-HAPLN1 group exhibited a decrease in the M1/Mϕ ratio and inflammatory factor expression. Notably, the introduction of rHAPLN1 in rescue experiments further promoted Mϕ polarization towards the M1 phenotype. Conclusion HAPLN1, secreted by RA fibroblast-like synoviocytes (RA-FLS), enhances Mϕ polarization towards the M1 phenotype.
Humans ; Arthritis, Rheumatoid/genetics* ; Macrophages/immunology* ; Fibroblasts/metabolism* ; Phenotype ; Extracellular Matrix Proteins/genetics* ; Proteoglycans/genetics* ; Synovial Membrane/cytology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; Nitric Oxide Synthase Type II/genetics* ; Cell Differentiation ; Coculture Techniques ; THP-1 Cells

OBJECTIVE: To observe the clinical efficacy of acupoint magnetotherapy as an adjunctive treatment for mild to moderate hypertension with yin deficiency and yang hyperactivity. METHODS: A total of 66 patients with mild to moderate hypertension of yin deficiency and yang hyperactivity were randomly divided into a magnetotherapy group (33 cases, 3 cases dropped out) and a non-magnetotherapy group (33 cases, 4 cases dropped out). Both groups were given antihypertensive drugs based on their clinical conditions. The magnetotherapy group and the non-magnetotherapy group wore surface magnetic therapy bands with or without magnetic poles, respectively, at unilateral Neiguan (PC6) and Waiguan (TE5). Intervention was administered once daily, 8 h each time, for a continuous period of 4 weeks. Traditional Chinese Medicine (TCM) syndrome score, Du's hypertension quality of life (QOL) scale score, office blood pressure, and 24-hour ambulatory blood pressure were assessed before and after the intervention, and the clinical efficacy was evaluated after intervention. RESULTS: After the intervention, both groups showed reductions in TCM syndrome scores, office systolic blood pressure (SBP), and diastolic blood pressure (DBP) compared with those before intervention (P<0.001), and their Du's QOL scores increased (P<0.001). The magnetotherapy group had lower TCM syndrome score and office SBP and DBP than those in the non-magnetotherapy group (P<0.001), while Du's QOL score was higher (P<0.001). After the intervention, all 24-hour ambulatory blood pressure indexes in the magnetotherapy group were reduced compared with those before intervention (P<0.05); in the non-magnetotherapy group, 24-hour average diastolic blood pressure (24hDBP), nighttime average systolic blood pressure (nSBP), and nighttime average diastolic blood pressure (nDBP) were reduced (P<0.05). The 24-hour average systolic blood pressure (24hSBP), 24hDBP, daytime average systolic blood pressure (dSBP), daytime average diastolic blood pressure (dDBP), and nSBP after intervention in the magnetotherapy group were lower than those in the non-magnetotherapy group (P<0.05). The total effective rate in the magnetotherapy group was 93.3% (28/30), which was higher than 75.9% (22/29) in the non-magnetotherapy group (P<0.05). CONCLUSION Acupoint magnetotherapy as an adjunctive treatment for mild to moderate hypertension with yin deficiency and yang hyperactivity could effectively alleviate clinical symptoms and TCM syndromes, improve quality of life, and reduce blood pressure level.
Humans ; Male ; Female ; Middle Aged ; Acupuncture Points ; Hypertension/physiopathology* ; Adult ; Yin Deficiency/physiopathology* ; Aged ; Blood Pressure ; Magnetic Field Therapy ; Acupuncture Therapy ; Treatment Outcome ; Combined Modality Therapy

The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Objective To understand the molecular epidemiological characteristics of Norovirus outbreaks and the genome evolution of Norovirus epidemic strains in Hainan Province from 2020 to 2022.Methods The information and samples have been collected from the norovirus outbreaks from 2020 to 2022.Norovirus was detected by using the real-time PCR in these samples,then the detected sequences were amplified the analyzed.The Norovirus se-quences of 8 strains had been amplified and analyzed.Results From 2020 to 2022,39 gastroenteritis outbreaks were reported,and 25 outbreaks caused by Norovirus which mainly occurred in childcare institutions and schools(20/25,80％).The Norovirus outbreaks were mainly concentrated in counties around Haikou(northeast),which including Ding'an(5 cases),Wenchang(4 cases),Chengmai(4 cases),and Lingao(3 cases);following by western regions which included Baisha(2 cases),Ledong(2 cases),and Dongfang(3 cases).1 case was in Wanning in the southeast.Among individuals aged 2-17,the positive proportion of Norovirus in males was higher than that in females.Among individuals aged over 55,the proportion of Norovirus positive in females was higher than that in males.The gender of positive samples among individuals aged 18-40 was related to their profession.According to RT-PCR typing and sequencing,GⅡ group Norovirus were classified in13 outbreaks.There were 4 genotypes detected.GⅡ.2[P1 6]was the main epidemic strain with 60％(9/13),and the other three genotypes were GⅡ.4 Sydney[P31](15.4％,2/13)GⅡ.4 Sydney[P16](7.7％,1/13)and GⅡ.3[P12](7.7％,1/13).Further genic analysis of 8 Norovirus strains showed that all of them were still in the same branch as the previ-ous strain,and all exhibited a certain amount of amino acid variation.Conclusion Norovirus is the main pathogen of gastroenteritis outbreaks in Hainan province,and the main epidemic strain is GⅡ.2[P16].It is necessary to continue to strengthen the monitoring that provides scientific evidence for the prevention and control of norovirus out-breaks in Hainan region.

Based on the Delphi method, combined with the results of the previous literature study and expert interviews, 3 rounds of expert consultation were conducted to evaluate the degree of concentration of expert opinions and their importance from 3 aspects: arithmetic mean, full score ratio ( Ki), and rank sum ( Si), to construct a diagnostic scale for rheumatoid arthritis (RA) cold-dampness syndrome. In this study, 30 expert questionnaires were distributed in the 1st round, 30 questionnaires were recovered, and the expert coordination coefficient was 0.309; 30 expert questionnaires were distributed in the 2nd round, 30 questionnaires were recovered, and the expert coordination coefficient was 0.320; and 30 expert questionnaires were distributed in the 3rd round, 29 questionnaires were recovered, and the expert coordination coefficient was 0.387. The maximum value of the coefficient of variation of the experts of the 3 rounds was 0.27, and the minimum value was 0.09, suggesting that the consistency and credibility of the experts' evaluation of the importance of the entries of cold-dampness syndrome were high. In this study, the mean values and weights of 17 entries were finally obtained, of which the top 5 entries were cold pain in joints (4.793, 0.066 6); aggravated by cold (4.586, 0.063 7); white tongue coating (4.552, 0.063 2); aggravated in cloudy and rainy days (4.448, 0.061 8); and painful joints that are not warm to the touch (4.379, 0.060 8). This study completed the screening of relevant entries and conducted preliminary discussions, laying the foundation for constructing a diagnostic scale for RA cold-dampness syndrome and forming the final diagnostic criteria. The research method is scientific and reliable, which can provide reference for the diagnostic standard of RA cold-dampness syndrome, but further clinical practice research is still needed.

Background Previous research indicated that isomers and alternatives of per- and polyfluoroalkyl substances (PFAS) probably disturb glucose metabolism; however, current epidemiological evidence on the associations of PFAS with fasting blood glucose is inconsistent. Besides, studies on the joint association of multiple components of PFAS and fasting blood glucose as well as the key component are scarce. Objective To evaluate the associations of PFAS isomers and alternatives with fasting blood glucose and their joint effects, as well as identify the key component among population without glucose metabolism problems. Methods We selected 923 adults without glucose metabolism problems or missing data from the Isomers of C8 Health Project in China (2015—2016). Serum PFAS isomers and alternatives and fasting blood glucose were measured using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) and automatic biochemical analyzer. We applied multiple linear regression to explore the associations of 16 pollutants which were detected among over 80% participants with fasting blood glucose. Meanwhile, we utilized qgcomp and Bayesian kernel machine regression (BKMR) models to explore the joint effects of PFAS isomers and alternatives mixture on target outcome indicators and identify the key component. Results The average age among the 923 participants in this study was (62.4±13.8) years old, including 472 men (51.1%) and 451 women (48.9%). Among selected PFAS isomers and alternatives, the highest serum concentration was ∑3+4+5m-PFOS (perfluoro-3/4/5-methylheptanesulfonate) with a median concentration of 10.20 ng·mL⁻¹. The concentrations of linear perfluorooctane sulfonate (n-PFOS, 9.61 ng·mL⁻¹), perfluorooctanoic acid (PFOA, 4.55 ng·mL⁻¹), linear perfluorohexane sulfonic acid (n-PFHxS, 2.48 ng·mL⁻¹), 6:2 chlorinated polyfluorinated ethersulfonic acid (6:2 Cl-PFESA, 1.90 ng·mL⁻¹), perfluoro-6-methylheptanesulfonate (iso-PFOS, 1.85 ng·mL⁻¹), perfluorobutanoic acid (PFBA, 1.81 ng·mL⁻¹), perfluorinated n-nonanoic acid (PFNA, 1.39 ng·mL⁻¹), and perfluoro-1-methylheptanesulfonate (1m-PFOS, 1.27 ng·mL⁻¹) were higher than 1.00 ng·mL⁻¹. After being adjusted for selected confounders, PFAS isomers and alternatives were positively associated with fasting blood glucose. With 1 ln unit concentration increment of 6:2 Cl-PFESA and PFNA, the estimated changes of fasting blood glucose were 0.18 (95%CI: 0.13, 0.23) mmol·L⁻¹ and 0.24 (95%CI: 0.18, 0.30) mmol·L⁻¹, respectively. The multi-pollutant models indicated a joint association of PFAS isomers and alternatives mixture with fasting blood glucose. The BKMR models reveals that as the quantiles of mixture elevated from the 50^th to the 75^th percentile, the values of fasting blood glucose increased 0.25 (95%CI: 0.21, 0.30) mmol·L⁻¹, and the posterior inclusion probability of PFNA was 0.92, implying that PFNA was the key component. Conclusion PFAS isomers and alternatives are positively associated with fasting blood glucose. PFNA is the key component of the joint association.

Objective:To analyze the dosimetric differences of volumetric modulated arc therapy (VMAT) plans for lung cancer caused by different dose calculation algorithms and radiation field settings and thus to provide a reference for designing clinical VMAT plans for lung cancer.Methods:This study randomly selected 20 patients with lung cancer and divided them into four groups of VMAT plans, namely, a group adopting two fields and two arcs based on the AAA algorithm (2F2A_AAA), a group employing two fields and two arcs based on the AXB algorithm (2F2A_AXB), a group using two fields and two arcs based on the MC algorithm (2F2A_MC), and a group adopting one field and two arcs based on the MC algorithm (1F2A_MC). Then, this study evaluated the target coverage, high-dose control, dose homogeneity index (HI), conformity index (CI), and organs at risk (OARs) of the plans using different algorithms and radiation field settings.Results:The planning target volume (PTV) results of two fields combined with two arcs (2F2A) of three groups using different algorithms are as follows. 2F2A_MC achieved better results in both D1% and V 95% (the relative volume of the target volume surrounded by 95% of the prescribed dose) of planning gross target volume (PGTV) than 2F2A_AAA (D1%: t=-2.44, P=0.03; V95%:z=-2.04, P=0.04) and 2F2A_AXB (D1%: t=2.34, P=0.03; z=-3.21, P < 0.01). 2F2A_AXB outperformed 2F2A_AAA ( z=-3.66, P < 0.01) and was comparable to 2F2A_MC in terms of the CI of PGTV. Regarding OARs, 2F2A_AXB and 2F2A_MC decreased the V5 Gy of the whole lung by 0.68% ( z=-2.69, P=0.01) and 3.05% ( z=-3.52, P < 0.01), respectively compared to 2F2A_AAA. 2F2A_AXB achieved a whole-lung Dmean of 1776.44 cGy, which was superior to that of 2F2A_MC ( t=2.67, P=0.02) and 2F2A_AAA ( t=8.62, P < 0.01). Compared to 2F2A_AAA and 2F2A_MC, 2F2A_AXB decreased the V20 Gy of Body_5 mm by 1.45% ( z=-3.88, P < 0.01) and 2.01% ( z=-3.66, P < 0.01), respectively. The results of the two groups with different field settings showed that 1F2A_MC was superior to 2F2A_MC in both the CI of PTV1 and the HI of PTV2 (CI: t=2.61, P=0.02; HI: z=-2.20, P=0.03). Moreover, 1F2A_MC increased the Dmean of the whole lung by 26.29 cGy compared to 2F2A_MC ( t=2.28, P=0.04). Conclusions:Regarding the design of VMAT plans for lung cancer, the MC algorithm is suitable for the target priority and the AXB algorithm is suitable for the OAR priority. When only the MC algorithm is available, it is recommended to choose 1F2A in the case of target priority and select 2F2A in the case of OAR priority.

Objective To explore the effective management of post-operation infections through clinical pharmacists participating in the treatment of a gastric cancer patient with post operation abdominal infection and cellulitis. Methods Clinical pharmacists provided an rational anti-infective treatment plan with the combination of pharmacy and clinical practice, conducted medication education for the patient, and participated in the process of pharmacy care for the patient. Results Physicians modified the medication plan according to the recommendations from the clinical pharmacists. The patient’s infection was effectively controlled and the symptoms were alleviated. Conclusion With their professional knowledge, clinical pharmacists can select the best antibacterial drug regimen for the treatment of post-operation infections and provide patients with optimal pharmaceutical care.

The loss of endothelial connective integrity and endothelial barrier dysfunction can lead to increased vascular injury, which is related to the activation of endothelial inflammasomes. There are evidences that low concentrations of aspirin can effectively prevent cardiovascular diseases. We hypothesized that low-dose aspirin could ameliorate endothelial injury by inhibiting the activation of NLRP3 inflammasomes and ultimately prevent cardiovascular diseases. Microvascular endothelial cells were stimulated by lipopolysaccharide (2 μg/mL) and administrated by 0.1-2 mmol/L aspirin. The wild type mice were stimulated with LPS (100 μg/kg/day), and 1 h later treated with aspirin (12.5, 62.5, or 125 mg/kg/day) and dexamethasone (0.0182 mg/kg/day) for 7 days. Plasma and heart were harvested for measurement of ELISA and immunofluorescence analyses. We found that aspirin could inhibit NLRP3 inflammasome formation and activation in dose-dependent manner and has correlation between the NLRP3 inflammasome and the ROS/TXNIP pathway. We also found that low-concentration aspirin could inhibit the formation and activation of NLRP3 inflammasome and restore the expression of the endothelial tight junction protein zonula occludens-1/2 (ZO1/2). We assume that aspirin can ameliorate the endothelial layer dysfunction by suppressing the activation of NLRP3 inflammasome.

Objective: To investigate the status of self-measurement of body weight in overweight and obese adults in China and identify the related factors. Methods: A total of 87 670 adults were enrolled in this study, who were selected through multi stage cluster random sampling from 177 099 residents aged ≥18 years in 302 surveillance areas in China where the fourth chronic non-communicable disease and related factor surveillance project was conducted in 2013. The information about their demographic characteristics and body weight measurement were collected by using questionnaire. Their body height, body weight, waist circumstance and blood pressure were measured respectively through physical examination. Fasting venous blood samples were obtained and assayed for FPG, TC, TG, LDL-C and HDL-C levels. Venous blood samples after 75 g glucose intake were obtained and assayed for OGTT-2h level. The proportion of self-body weight measurement were analyzed after complex sample weighting. Results: The proportion of overweight and obese adults who had self-body weight measurement within 1 week, 1 month and 1 year were 18.9%, 23.0% and 30.2%, respectively. The proportion of those having self-body weight measurement within 1 week was higher in men than in women, and lowest in ≥60 years old group (P<0.05). The proportion of overweight and obese adults who had never measured their body weight was 20.5%, the proportion was higher in women than in men, and highest in ≥60 years old group (P<0.05). Older age (OR=0.73, 95%CI: 0.64-0.82) was risk factor for self-body weight measurement; female (OR=1.11, 95%CI: 1.03-1.19), higher education level (junior college and above OR=3.79, 95%CI: 2.89-4.97), high- income (OR=1.61, 95%CI: 1.31-1.98), dyslipidemia (OR=1.13, 95%CI: 1.04-1.23), diabetes (OR=1.15, 95%CI: 1.03-1.30) were the protective factors for self-body weight measurement. Conclusion It is necessary to promote self-body weight measurement in overweight and obese adults in China. Targeted health education should be carried out for different groups to encourage regular self-body weight measurement to maintain healthy body weight.