ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

Background: Maintenance of stable blood pressure (BP) during cerebrovascular bypass surgery is crucial to prevent cerebral ischemia. We compared the effect of remimazolam anesthesia with that of propofol-induced and desflurane-maintained anesthesia on intraoperative hemodynamic stability and the need for vasoactive agents in patients undergoing cerebrovascular bypass surgery. Methods: Sixty-five patients were randomized into remimazolam (n = 31, remimazolam-based intravenous anesthesia) and control groups (n = 34, propofol-induced and desflurane-maintained anesthesia). The primary outcome was the occurrence of intraoperative hypotension. The secondary outcomes included hypotension duration, lowest mean BP (MBP), generalized average real variability (ARV) of MBP, and consumption of phenylephrine, norepinephrine, or remifentanil. Results: Occurrence rate and duration of hypotension were significantly lower in the remimazolam group (38.7% vs. 73.5%, P = 0.005; 0 [0, 10] vs. 7.5 [1.25, 25] min, P = 0.008). Remimazolam also showed better outcomes for lowest MBP (78 [73, 84] vs. 69.5 [66.25, 75.8] mmHg, P < 0.001) and generalized ARV of MBP (1.42 ± 0.49 vs. 1.66 ± 0.52 mmHg/min, P = 0.036). The remimazolam group required less phenylephrine (20 [0, 65] vs. 100 [60, 130] μg, P < 0.001), less norepinephrine (162 [0, 365.5] vs. 1335 [998.5, 1637.5] μg, P < 0.001), and more remifentanil (1750 [1454.5, 2184.5] vs. 531 [431, 746.5] μg, P < 0.001) than the control group. Conclusions Remimazolam anesthesia may provide better hemodynamic stability during cerebrovascular bypass surgery than propofol-induced and desflurane-maintained anesthesia.

Background: Maintenance of stable blood pressure (BP) during cerebrovascular bypass surgery is crucial to prevent cerebral ischemia. We compared the effect of remimazolam anesthesia with that of propofol-induced and desflurane-maintained anesthesia on intraoperative hemodynamic stability and the need for vasoactive agents in patients undergoing cerebrovascular bypass surgery. Methods: Sixty-five patients were randomized into remimazolam (n = 31, remimazolam-based intravenous anesthesia) and control groups (n = 34, propofol-induced and desflurane-maintained anesthesia). The primary outcome was the occurrence of intraoperative hypotension. The secondary outcomes included hypotension duration, lowest mean BP (MBP), generalized average real variability (ARV) of MBP, and consumption of phenylephrine, norepinephrine, or remifentanil. Results: Occurrence rate and duration of hypotension were significantly lower in the remimazolam group (38.7% vs. 73.5%, P = 0.005; 0 [0, 10] vs. 7.5 [1.25, 25] min, P = 0.008). Remimazolam also showed better outcomes for lowest MBP (78 [73, 84] vs. 69.5 [66.25, 75.8] mmHg, P < 0.001) and generalized ARV of MBP (1.42 ± 0.49 vs. 1.66 ± 0.52 mmHg/min, P = 0.036). The remimazolam group required less phenylephrine (20 [0, 65] vs. 100 [60, 130] μg, P < 0.001), less norepinephrine (162 [0, 365.5] vs. 1335 [998.5, 1637.5] μg, P < 0.001), and more remifentanil (1750 [1454.5, 2184.5] vs. 531 [431, 746.5] μg, P < 0.001) than the control group. Conclusions Remimazolam anesthesia may provide better hemodynamic stability during cerebrovascular bypass surgery than propofol-induced and desflurane-maintained anesthesia.

Background: Maintenance of stable blood pressure (BP) during cerebrovascular bypass surgery is crucial to prevent cerebral ischemia. We compared the effect of remimazolam anesthesia with that of propofol-induced and desflurane-maintained anesthesia on intraoperative hemodynamic stability and the need for vasoactive agents in patients undergoing cerebrovascular bypass surgery. Methods: Sixty-five patients were randomized into remimazolam (n = 31, remimazolam-based intravenous anesthesia) and control groups (n = 34, propofol-induced and desflurane-maintained anesthesia). The primary outcome was the occurrence of intraoperative hypotension. The secondary outcomes included hypotension duration, lowest mean BP (MBP), generalized average real variability (ARV) of MBP, and consumption of phenylephrine, norepinephrine, or remifentanil. Results: Occurrence rate and duration of hypotension were significantly lower in the remimazolam group (38.7% vs. 73.5%, P = 0.005; 0 [0, 10] vs. 7.5 [1.25, 25] min, P = 0.008). Remimazolam also showed better outcomes for lowest MBP (78 [73, 84] vs. 69.5 [66.25, 75.8] mmHg, P < 0.001) and generalized ARV of MBP (1.42 ± 0.49 vs. 1.66 ± 0.52 mmHg/min, P = 0.036). The remimazolam group required less phenylephrine (20 [0, 65] vs. 100 [60, 130] μg, P < 0.001), less norepinephrine (162 [0, 365.5] vs. 1335 [998.5, 1637.5] μg, P < 0.001), and more remifentanil (1750 [1454.5, 2184.5] vs. 531 [431, 746.5] μg, P < 0.001) than the control group. Conclusions Remimazolam anesthesia may provide better hemodynamic stability during cerebrovascular bypass surgery than propofol-induced and desflurane-maintained anesthesia.

Background: Maintenance of stable blood pressure (BP) during cerebrovascular bypass surgery is crucial to prevent cerebral ischemia. We compared the effect of remimazolam anesthesia with that of propofol-induced and desflurane-maintained anesthesia on intraoperative hemodynamic stability and the need for vasoactive agents in patients undergoing cerebrovascular bypass surgery. Methods: Sixty-five patients were randomized into remimazolam (n = 31, remimazolam-based intravenous anesthesia) and control groups (n = 34, propofol-induced and desflurane-maintained anesthesia). The primary outcome was the occurrence of intraoperative hypotension. The secondary outcomes included hypotension duration, lowest mean BP (MBP), generalized average real variability (ARV) of MBP, and consumption of phenylephrine, norepinephrine, or remifentanil. Results: Occurrence rate and duration of hypotension were significantly lower in the remimazolam group (38.7% vs. 73.5%, P = 0.005; 0 [0, 10] vs. 7.5 [1.25, 25] min, P = 0.008). Remimazolam also showed better outcomes for lowest MBP (78 [73, 84] vs. 69.5 [66.25, 75.8] mmHg, P < 0.001) and generalized ARV of MBP (1.42 ± 0.49 vs. 1.66 ± 0.52 mmHg/min, P = 0.036). The remimazolam group required less phenylephrine (20 [0, 65] vs. 100 [60, 130] μg, P < 0.001), less norepinephrine (162 [0, 365.5] vs. 1335 [998.5, 1637.5] μg, P < 0.001), and more remifentanil (1750 [1454.5, 2184.5] vs. 531 [431, 746.5] μg, P < 0.001) than the control group. Conclusions Remimazolam anesthesia may provide better hemodynamic stability during cerebrovascular bypass surgery than propofol-induced and desflurane-maintained anesthesia.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

The MADS-box gene family is a very important transcriptional regulator gene, which plays a role in the whole growth and development process of plants. The APETALA1 (AP1) gene is considered to play an important regulatory role in the transformation of plant flowering, but also to control the characteristic development of floral organs. Lonicera macranthoides is used as medicine with dry buds and early flowers. Therefore, studying the potential mechanism of AP1 gene in regulating flower organ development can provide a basis for improving its medicinal value by molecular means. To explore the potential mechanism of the AP1 gene in the regulation of floral organ development in L. macranthoides, the full-length cDNA of the AP1 was cloned by reverse transcription PCR (RT-PCR) and named LmMADS4. The results show that the CDS of the LmMADS4 gene is 729 bp and encodes 242 amino acids, and the LmMADS4 protein contains no signal peptide and no transmembrane structure, which is an unstable hydrophilic protein. Through homologous sequence alignment and phylogenetic analysis, LmMADS4 and L. japonica MADS27 protein cluster into one class and are closely related. Finally, the expression pattern and protein interaction pattern of LmMADS4 were analyzed by real-time reverse transcription-PCR (qRT-PCR) and yeast two-hybrid technology. The qRT-PCR showed that LmMADS4 gene was differentially expressed in the stems, leaves and flower bud at different developmental stages, including bud type variety Longhua and common variety Baiyun; and LmMADS4 gene was highly expressed in the flower buds, and with the development of flower buds, LmMADS4 gene was continuously up-regulated in the flower bud variety Longhua, however, the expression level of LmMADS4 in the Baiyun terminal flower bud was lower than that in the late flower bud, but the difference was not significant. The yeast two-hybrid results showed that the bait vector pGBKT7-LmMADS4 was not toxic to yeast strains and had no self-activating activity. LmMADS4 protein interacted with LmSVP1, LmSVP3 and LmSOC1s proteins. This study can provide a theoretical basis for exploring the mechanism of long flower bud stage and corolla non-unfolding at the molecular level and variety improvement of L. macranthoides.

Objective To investigate the therapeutic effect of transcutaneous auricular vagus nerve stimulation(taVNS)on overweight/obesity patients,and to explore its central mechanism.Methods Twenty-six overweight/obesity patients were randomly divided into two groups,12 cases in the taVNS test group(shortened as the taVNS group)and 14 cases in the lifestyle intervention control group(shortened as the control group).The patients in the control group were treated with online lifestyle intervention of calorie-restricted diet(CRD),and the patients in the taVNS group were treated with taVNS on the basis of the intervention for the control group.The taVNS was performed on unilateral acupoints of spleen and endocrine,twice(in the morning and at evening)per day,for five days a week.The treatment for the two groups covered four weeks.The obesity indicators such as body weight,body mass index(BMI)and waist circumference of the patients in the two groups were observed before and after treatment.Moreover,the resting-state cerebral functional magnetic resonance imaging(fMRI)data of the patients were collected after treatment,and then the regulatory effect of taVNS on the regional homogeneity(ReHo)of local cerebral area of the patients was observed.Results(1)During the trial,one case in each group dropped off,and a total of 24 patients(including 13 cases in the control group and 11 cases in the taVNS group)were finally included in the statistical analysis of the observation indicators.(2)After treatment,the body weight,BMI and waist circumference of patients in the taVNS group were decreased compared with those before treatment(P＜0.05),while the obesity indicators in the control group only showed a downward trend compared with those before treatment,the differences being not statistically significant(P＞0.05).The improvement of the obesity indicators of body weight,BMI,and waist circumference in the taVNS group was significantly superior to that in the control group,and there were statistically significant differences in the post-treatment indicators and in the pre-and post-treatment difference values of the indicators between the two groups(P＜0.05 or P＜0.01).(3)After treatment,the taVNS group had greater ReHo values in the left prefrontal lobe and medial frontal gyrus than the control group,and the control group had greater ReHo value in the right parietal lobe than the taVNS group,which indicated that compared with the control group,the ReHo of the left prefrontal lobe and medial frontal gyrus in the taVNS group was increased and the ReHo of the right parietal lobe was decreased(Pvoxel＜0.001,Pcluster＜0.05,corrected by FWE level).Conclusion As a non-invasive treatment method,taVNS exerts certain efficacy for the treatment of overweight/obesity patients.The central response mechanism for treatment of obesity is probably related with the modulation of taVNS on the functional areas of left prefrontal lobe,medial frontal gyrus,and right parietal lobe of the patients.

Objective To investigate the efficacy and safety of subcutaneous immunotherapy(SCIT)using dust mites in children with allergic asthma.Methods In a prospective randomized controlled study,98 children with dust mite-induced allergic asthma were randomly divided into a control group(n=49)and an SCIT group(n=49).The control group received inhaled corticosteroid treatment,while the SCIT group additionally received a standardized three-year SCIT regimen.The two groups were compared based on peripheral blood eosinophil percentage,visual analogue score(VAS),total medication score,Asthma Control Test/Childhood Asthma Control Test scores,fractional exhaled nitric oxide(FeNO),and lung function before treatment,and at 6 months,1 year,2 years,and 3 years after treatment.Adverse reactions were recorded post-injection to evaluate the safety of SCIT.Results Compared with pre-treatment levels,the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils,VAS,total medication score,and FeNO,while lung function significantly improved,and asthma control levels were better 3 years after treatment(P<0.05).Compared with the control group,the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment(P<0.05).A total of 2 744 injections were administered,resulting in 157 cases(5.72%)of local adverse reactions and 4 cases(0.15%)of systemic adverse reactions,with no severe systemic adverse events.Conclusions SCIT is an effective and safe treatment for allergic asthma in children.

Background: To evaluate the degree of deformation in patients with ankle osteoarthritis (OA), it is essential to measure the threedimensional (3D), in other words, stereoscopic alignment of the ankle, subtalar, and foot arches. Generally, measurement of radiological parameters use two-dimensional (2D) anteroposterior and lateral radiographs in a weight-bearing state; however, computeraided 3D analysis (Disior) using weight-bearing cone-beam computed tomography (CBCT) has recently been introduced. Methods: In this study, we compared the 2D human radiographic method with a stereoscopic image in patients with ankle arthritis. We enrolled 57 patients diagnosed with OA (28 left and 29 right) and obtained both standing radiographs and weight-bearing CBCT. Patients were divided by the Takakura stage. The interclass correlation coefficient (ICC) for each result was confirmed. Results: On the ICC between 2D radiographs and 3D analysis, the tibiotalar surface angle and lateral talo-1st metatarsal angle showed a good ICC grade (> 0.6), while other parameters did not have significant ICC results. Three-dimension was superior to radiographs in terms of statistical significance. Conclusions We demonstrated that 2D and stereoscopic images are useful for the diagnosis of OA. Our study also confirmed that the radiographic features affected by ankle OA varied. However, according to the results, the typical radiography is not sufficient to diagnose and determine a treatment plan for ankle OA. Therefore, the method of using 3D images should be considered.