Background::Statins are the first line of treatment for dyslipidemia, but their side effects often reduce medication compliance. Natto and red yeast rice are natural ingredients with lipid-lowering effects. However, the efficacy of Natto Red Yeast Rice (NRYR) supplement in combination with statins in regulating blood lipid levels has not been fully evaluated.Methods::A multicenter, double-blinded, randomized-controlled trial was conducted among individuals with low-density lipoprotein cholesterol (LDL-C) of 3.4 to 5.0 mmol/L at six sites in China, of those at moderate risk of cardiovascular disease (CVD) are prioritized. Participants are enrolled and randomly assigned into four groups by a combination of NRYR (or its placebo) and Simvastatin (or its placebo) in a ratio of 1:1:1:1. After examination at baseline, all participants underwent intervention for 3 months and two follow-up visits at 1 month and 3 months after the intervention. The primary outcome is the change in LDL-C level at 3 months, and secondary outcomes include changes in levels of other lipid profiles and biomarkers, as well as calculated 10-year CVD risk. A total of 1136 participants were randomly assigned, of whom 1110 received the intervention.Discussion::This study may provide new evidence for the efficacy of NRYR supplement in combination with statins to regulate lipid levels and optimize lipid management.Trial Registration::Chinese Clinical Trial Registry database: registration nos. ChiCTR2200064214, ChiCTR2200064215.

Objective:To compare the efficacy of intranasal nebulized remimazolam versus esketamine for preoperative sedation in pediatric patients.Methods:In this randomized double-blind controlled trial, 90 pediatric patients scheduled for elective surgery with general anesthesia at Fuyang People′s Hospital between October 2024 and January 2025, were divided into 3 groups ( n=30 each) using a simple randomization: remimazolam group (group R), esketamine group (group S) and normal saline group (group C). Group R received intranasal nebulization of remimazolam 1.5 mg/kg, group S received intranasal nebulization of esketamine 1 mg/kg, and group C received intranasal nebulization of normal saline 0.05 ml/kg. Primary outcome: The preoperative anxiety was assessed using the modified Yale Preoperative Anxiety Scale before intranasal drug administration (baseline), at 10 and 20 min after administration, and before anesthesia induction. Secondary outcomes included sedation level (Ramsay Sedation Scale score), satisfaction with intranasal administration acceptance, parental separation anxiety and mask acceptance, development of emergence agitation, emergence time, time of recovery from anesthesia, and nausea and vomiting and increased secretions. Results:Compared to group C, the incidence of anxiety was significantly decreased at 10 and 20 min after intranasal nebulization and before anesthesia induction, the level of sedation was deepened (to light sedation), and the satisfaction with intranasal administration acceptance was decreased in group R ( P<0.017), the incidence of anxiety was significantly decreased before anesthesia induction, the level of sedation was deepened (to deep sedation), and the satisfaction with intranasal administration acceptance was increased in group S ( P<0.017), and the satisfaction with parental separation anxiety and mask acceptance and anesthesiologists′ satisfaction were significantly increased in R and S groups( P<0.017). Compared to group R, the incidence of anxiety was significantly increased at 10 min after intranasal nebulization (7 cases [23%] versus 20 cases [67%]), the level of sedation was lighter at 10 min after intranasal nebulization, the level of sedation was deeper, and the satisfaction with intranasal administration acceptance was increased in group S ( P<0.017). Compared to groups C and R, the emergence time and time of recovery from anesthesia were significantly prolonged in group S ( P<0.017). There was no significant difference in the incidence of emergence agitation, nausea and vomiting and increased secretions or in parental satisfaction among three groups ( P>0.05). Conclusions:Both intranasal nebulized remimazolam and esketamine can produce good preoperative sedation in pediatric patients. Compared to esketamine, remimazolam provides a more appropriate level of sedation with a faster onset and does not prolong the recovery from anesthesia, making it more suitable for preoperative sedation in minor procedures.

Background::Statins are the first line of treatment for dyslipidemia, but their side effects often reduce medication compliance. Natto and red yeast rice are natural ingredients with lipid-lowering effects. However, the efficacy of Natto Red Yeast Rice (NRYR) supplement in combination with statins in regulating blood lipid levels has not been fully evaluated.Methods::A multicenter, double-blinded, randomized-controlled trial was conducted among individuals with low-density lipoprotein cholesterol (LDL-C) of 3.4 to 5.0 mmol/L at six sites in China, of those at moderate risk of cardiovascular disease (CVD) are prioritized. Participants are enrolled and randomly assigned into four groups by a combination of NRYR (or its placebo) and Simvastatin (or its placebo) in a ratio of 1:1:1:1. After examination at baseline, all participants underwent intervention for 3 months and two follow-up visits at 1 month and 3 months after the intervention. The primary outcome is the change in LDL-C level at 3 months, and secondary outcomes include changes in levels of other lipid profiles and biomarkers, as well as calculated 10-year CVD risk. A total of 1136 participants were randomly assigned, of whom 1110 received the intervention.Discussion::This study may provide new evidence for the efficacy of NRYR supplement in combination with statins to regulate lipid levels and optimize lipid management.Trial Registration::Chinese Clinical Trial Registry database: registration nos. ChiCTR2200064214, ChiCTR2200064215.

Objective:To compare the efficacy of intranasal nebulized remimazolam versus esketamine for preoperative sedation in pediatric patients.Methods:In this randomized double-blind controlled trial, 90 pediatric patients scheduled for elective surgery with general anesthesia at Fuyang People′s Hospital between October 2024 and January 2025, were divided into 3 groups ( n=30 each) using a simple randomization: remimazolam group (group R), esketamine group (group S) and normal saline group (group C). Group R received intranasal nebulization of remimazolam 1.5 mg/kg, group S received intranasal nebulization of esketamine 1 mg/kg, and group C received intranasal nebulization of normal saline 0.05 ml/kg. Primary outcome: The preoperative anxiety was assessed using the modified Yale Preoperative Anxiety Scale before intranasal drug administration (baseline), at 10 and 20 min after administration, and before anesthesia induction. Secondary outcomes included sedation level (Ramsay Sedation Scale score), satisfaction with intranasal administration acceptance, parental separation anxiety and mask acceptance, development of emergence agitation, emergence time, time of recovery from anesthesia, and nausea and vomiting and increased secretions. Results:Compared to group C, the incidence of anxiety was significantly decreased at 10 and 20 min after intranasal nebulization and before anesthesia induction, the level of sedation was deepened (to light sedation), and the satisfaction with intranasal administration acceptance was decreased in group R ( P<0.017), the incidence of anxiety was significantly decreased before anesthesia induction, the level of sedation was deepened (to deep sedation), and the satisfaction with intranasal administration acceptance was increased in group S ( P<0.017), and the satisfaction with parental separation anxiety and mask acceptance and anesthesiologists′ satisfaction were significantly increased in R and S groups( P<0.017). Compared to group R, the incidence of anxiety was significantly increased at 10 min after intranasal nebulization (7 cases [23%] versus 20 cases [67%]), the level of sedation was lighter at 10 min after intranasal nebulization, the level of sedation was deeper, and the satisfaction with intranasal administration acceptance was increased in group S ( P<0.017). Compared to groups C and R, the emergence time and time of recovery from anesthesia were significantly prolonged in group S ( P<0.017). There was no significant difference in the incidence of emergence agitation, nausea and vomiting and increased secretions or in parental satisfaction among three groups ( P>0.05). Conclusions:Both intranasal nebulized remimazolam and esketamine can produce good preoperative sedation in pediatric patients. Compared to esketamine, remimazolam provides a more appropriate level of sedation with a faster onset and does not prolong the recovery from anesthesia, making it more suitable for preoperative sedation in minor procedures.

Fibromyalgia syndrome （FMS） is a refractory， chronic non-articular rheumatic disease characterized by widespread pain throughout the body， for which there are no satisfactory therapeutic drugs or options. There are rich Chinese medical therapies， and some non-drug therapies， such as acupuncture， Tai Chi， and Ba-Duan-Jin， have shown satisfactory efficacy and safety and definite advantages of simultaneously adjusting mind and body. FMS is taken as a disease responding specifically to traditional Chinese medicine （TCM） by the National Administration of Traditional Chinese Medicine in 2018. In order to clarify the research progress in FMS and the clinical advantages of TCM/integrated Chinese and Western medicine， the China Academy of Chinese Medicine organized a seminar for nearly 20 experts in Chinese and Western medicine， including rheumatology， psychology， acupuncture and moxibustion， and encephalopathy， with the topic of difficulties in clinical diagnosis and treatment of FMS and advantages of TCM and Western medicine. The recommendations were reached on the difficulties in early diagnosis and solutions of FMS， mitigation of common non-specific symptoms， preferential analgesic therapy， TCM pathogenesis and treatment advantages， and direction of treatment with integrated Chinese and Western medicine. FMS is currently facing the triple dilemma of low early correct diagnosis， poor patient participation， and unsatisfactory benefit from pure Western medicine treatment. To solve the above problems， this paper suggests that rheumatologists should serve as the main diagnostic force of this disease， and they should improve patient participation in treatment decision-making， implement exercise therapy， and fully utilize the holistic and multidimensional features of TCM， which is effective in alleviating pain， improving mood， and decreasing adverse events. In addition， it is suggested that FMS treatment should rely on both TCM and Western medicine and adopt multidisciplinary joint treatment， which is expected to improve the standard of diagnosis and treatment of FMS in China.

Background:The core circadian clock gene Bmal1 has been shown to be involved in the formation of visceral sensitization in irritable bowel syndrome(IBS)by affecting the tryptophan hydroxylase 1(TPH1)-5-hydroxytryptamine(5-HT)pathway,but the exact mechanism of its regulation is unknown.Aims:To investigate the molecular mechanism by which Bmal1 regulates the TPH1-5-HT pathway through the clock-controlled gene Piezo1.Methods:Dexamethasone was used to synchronize the expression of the circadian clock genes in RIN-14B cells.Bmal1 expression was up-regulated or down-regulated in RIN-14B cells by plasmid and siRNA transfection of the enterochromaffin cell(EC)model.The expression levels of target genes and proteins were detected by immunofluorescence staining,RT-qPCR,and Western blotting.5-HT content was detected by ELISA method.Results:(1)This study was the first to report the oscillation characteristics of RIN-14B circadian clock genes in EC model,among which the oscillation of Bmal1 was the most significant.Immunofluorescence showed that RIN-14B cells expressed CGA,Bmal1 and Piezo1.(2)After transfected with the Bmal1 overexpression plasmid,the mRNA and protein expression of Bmal1 were significantly up-regulated in RIN-14B cells compared with the negative control group(all P<0.001);while transfected with Bmal1 siRNA significantly decreased the mRNA and protein expression of Bmal1 in RIN-14B cells compared with the negative control group(all P<0.05).(3)After transfected with Bmal1 overexpression plasmid,the mRNA and protein expression of Piezo1,the protein expression of TPH1,and the intracellular content of 5-HT were significantly increased(all P<0.051).(4)After transfected with Bmal siRNA,mRNA expression of Piezo1 and TPH1 in RIN-14B cells was significantly down-regulated(all P<0.05),and the protein expression of Piezo1,TPH1,the intracellular 5-HT content tended to be decreased by 21%,31%,and 10%,respectively.Conclusions:RIN-14B cells have the characteristics of rhythmic oscillation of circadian clock genes,and Bmal1 overexpression and underexpression EC models can be successfully established by using RIN-14B cells.Overexpression and underexpression of Bmal1 can lead to significant changes in the clock-controlled Piezo1-TPH1-5-HT signaling pathway,suggesting that Bmal1 can be expressed by clock-control signals through the Piezo1-TPH1 pathway.This suggests that Bmal1 may be involved in the development of visceral hypersensitivity in IBS through regulation of 5-HT synthesis by the clock-controlled gene Piezo1.

Background::Despite the adverse effects of ambient fine particulate matter (PM 2.5) on type 2 diabetes and the beneficial role of physical activity (PA), the influence of PM 2.5 on the relationship between PA and type 2 diabetes remains unclear. Methods::In this prospective study with 71,689 participants, PA was assessed by a questionnaire and was categorized into quartiles for volume and three groups for intensity. Long-term PM 2.5 exposure was calculated using 1-km resolution satellite-based PM 2.5 estimates. PM 2.5 exposure and PA's effect on type 2 diabetes were assessed by cohort-stratified Cox proportional hazards models, individually and in combination. Results::In 488,166 person-years of follow-up, 5487 incident type 2 diabetes cases were observed. The association between PA and type 2 diabetes was modified by PM 2.5. Compared with the lowest quartile of PA volume, the highest quartile was associated with reduced type 2 diabetes risk in low PM 2.5 stratification (≤65.02 μg/m 3) other than in high PM 2.5 stratification (>65.02 μg/m 3), with the hazard ratio (HR) of 0.75 (95% confidence interval [CI]: 0.66-0.85) and 1.10 (95% CI: 0.99-1.22), respectively. Similar results were observed for PA intensity. High PM 2.5 exposure combined with the highest PA levels increased the risk of type 2 diabetes the most (HR= 1.79, 95% CI: 1.59-2.01 for PA volume; HR = 1.82, 95% CI: 1.64-2.02 for PA intensity). Conclusion::PA could reduce type 2 diabetes risk in low-pollution areas, but high PM 2.5 exposure may weaken or even reverse the protective effects of PA. Safety and health benefits of PA should be thoroughly assessed for long-term polluted residents.

Background::Despite the adverse effects of ambient fine particulate matter (PM 2.5) on type 2 diabetes and the beneficial role of physical activity (PA), the influence of PM 2.5 on the relationship between PA and type 2 diabetes remains unclear. Methods::In this prospective study with 71,689 participants, PA was assessed by a questionnaire and was categorized into quartiles for volume and three groups for intensity. Long-term PM 2.5 exposure was calculated using 1-km resolution satellite-based PM 2.5 estimates. PM 2.5 exposure and PA's effect on type 2 diabetes were assessed by cohort-stratified Cox proportional hazards models, individually and in combination. Results::In 488,166 person-years of follow-up, 5487 incident type 2 diabetes cases were observed. The association between PA and type 2 diabetes was modified by PM 2.5. Compared with the lowest quartile of PA volume, the highest quartile was associated with reduced type 2 diabetes risk in low PM 2.5 stratification (≤65.02 μg/m 3) other than in high PM 2.5 stratification (>65.02 μg/m 3), with the hazard ratio (HR) of 0.75 (95% confidence interval [CI]: 0.66-0.85) and 1.10 (95% CI: 0.99-1.22), respectively. Similar results were observed for PA intensity. High PM 2.5 exposure combined with the highest PA levels increased the risk of type 2 diabetes the most (HR= 1.79, 95% CI: 1.59-2.01 for PA volume; HR = 1.82, 95% CI: 1.64-2.02 for PA intensity). Conclusion::PA could reduce type 2 diabetes risk in low-pollution areas, but high PM 2.5 exposure may weaken or even reverse the protective effects of PA. Safety and health benefits of PA should be thoroughly assessed for long-term polluted residents.

Background:The core circadian clock gene Bmal1 has been shown to be involved in the formation of visceral sensitization in irritable bowel syndrome(IBS)by affecting the tryptophan hydroxylase 1(TPH1)-5-hydroxytryptamine(5-HT)pathway,but the exact mechanism of its regulation is unknown.Aims:To investigate the molecular mechanism by which Bmal1 regulates the TPH1-5-HT pathway through the clock-controlled gene Piezo1.Methods:Dexamethasone was used to synchronize the expression of the circadian clock genes in RIN-14B cells.Bmal1 expression was up-regulated or down-regulated in RIN-14B cells by plasmid and siRNA transfection of the enterochromaffin cell(EC)model.The expression levels of target genes and proteins were detected by immunofluorescence staining,RT-qPCR,and Western blotting.5-HT content was detected by ELISA method.Results:(1)This study was the first to report the oscillation characteristics of RIN-14B circadian clock genes in EC model,among which the oscillation of Bmal1 was the most significant.Immunofluorescence showed that RIN-14B cells expressed CGA,Bmal1 and Piezo1.(2)After transfected with the Bmal1 overexpression plasmid,the mRNA and protein expression of Bmal1 were significantly up-regulated in RIN-14B cells compared with the negative control group(all P<0.001);while transfected with Bmal1 siRNA significantly decreased the mRNA and protein expression of Bmal1 in RIN-14B cells compared with the negative control group(all P<0.05).(3)After transfected with Bmal1 overexpression plasmid,the mRNA and protein expression of Piezo1,the protein expression of TPH1,and the intracellular content of 5-HT were significantly increased(all P<0.051).(4)After transfected with Bmal siRNA,mRNA expression of Piezo1 and TPH1 in RIN-14B cells was significantly down-regulated(all P<0.05),and the protein expression of Piezo1,TPH1,the intracellular 5-HT content tended to be decreased by 21%,31%,and 10%,respectively.Conclusions:RIN-14B cells have the characteristics of rhythmic oscillation of circadian clock genes,and Bmal1 overexpression and underexpression EC models can be successfully established by using RIN-14B cells.Overexpression and underexpression of Bmal1 can lead to significant changes in the clock-controlled Piezo1-TPH1-5-HT signaling pathway,suggesting that Bmal1 can be expressed by clock-control signals through the Piezo1-TPH1 pathway.This suggests that Bmal1 may be involved in the development of visceral hypersensitivity in IBS through regulation of 5-HT synthesis by the clock-controlled gene Piezo1.

Ganoderma lucidum is a valuable medical macrofungus with a myriad of diverse secondary metabolites, in which triterpenoids are the major constituents. This paper introduced the germplasm resources of genus Ganoderma from textual research, its distribution and identification at the molecular level. Also we overviewed G. lucidum in the components, the biological activities and biosynthetic pathways of ganoderic acid, aiming to provide scientific evidence for the development and utilization of G. lucidum germplasm resources and the biosynthesis of ganoderic acid.