1.The mechanism of SAP overexpression in alleviating periodontitis in mice
HUANG Yinyin ; LIANG Dongliang ; ZOU Yaokun ; HAN Jingru ; GE Qing ; LIU Xueyan ; GUO Yadong ; HUANG Xinli ; YANG Lan
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(8):619-630
Objective:
To investigate the mechanism by which serum amyloid P component (SAP) alleviates periodontitis in mice, providing an experimental basis to establish SAP as a novel therapeutic agent for periodontitis.
Methods:
Ethical approval was obtained from the Institutional Animal Ethics Committee. Periodontitis models were established in wild-type (WT) mice and SAP-transgenic (SAP-Tg) mice, divided into four groups: WT control (WT group), WT periodontitis (WT+P group), SAP-Tg control (Tg group), and SAP-Tg periodontitis (Tg+P group). On day 7, the mice were euthanized, and periodontal tissues, teeth, and alveolar bone were collected. SAP protein expression was detected by enzyme-linked immunosorbent assay (ELISA). Micro-CT and HE staining were used to measure alveolar bone resorption (distance from the cementoenamel junction to the alveolar bone crest). Tartrate-resistant acid phosphatase (TRAP) staining was performed to assess osteoclast number, and immunohistochemistry (IHC) was employed to evaluate macrophage infiltration. The expression levels of inflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured by qRT-PCR. Oral microorganism composition was analyzed using 16S ribosomal RNA (16S rRNA) gene sequencing. Additionally, macrophages from WT and SAP-Tg mice were isolated to establish an in vitro inflammation model, divided into WT+LPS and Tg+LPS groups. The expression of macrophage polarization-related genes including inducible nitric oxide synthase (iNOS), CD86, CD163, and CD206) were assessed by qRT-PCR. After the induction of osteoclast differentiation, TRAP staining was performed.
Results:
ELISA results demonstrated that periodontal tissues from Tg+P group mice exhibited higher levels of SAP expression compared to the WT+P group. Micro-CT and HE staining analyses revealed that the Tg+P group showed reduced alveolar bone resorption, indicated by a shorter distance between the cementoenamel junction and alveolar bone crest, compared to the WT+P group. Furthermore, TRAP staining results indicated a decrease in osteoclast numbers in the Tg+P group compared to the WT+P group. IHC and qRT-PCR results indicated reduced macrophage infiltration and decreased expression of IL-1β, IL-6, and TNF-α in the Tg+P group. Oral microorganism sequencing showed no significant difference in periodontitis-associated pathogenic bacteria between WT+P and Tg+P groups. In vitro experiments demonstrated that compared to the WT+LPS group, the Tg+LPS group exhibited downregulated M1 macrophage markers (iNOS and CD86) and upregulated M2 macrophage markers (CD163 and CD206). TRAP staining confirmed fewer osteoclasts in the Tg+LPS group.
Conclusion
SAP overexpression effectively alleviates periodontitis severity in mice by inhibiting M1 macrophage polarization, reducing pro-inflammatory cytokine expression, and suppressing osteoclast differentiation, thereby attenuating alveolar bone resorption.
2.Clinical Efficacy of Xiaoji Hufei Formula in Protecting Children with Close Contact Exposure to Influenza: A Multicenter,Prospective, Non-randomized, Parallel, Controlled Trial
Jing WANG ; Jianping LIU ; Tiegang LIU ; Hong WANG ; Yingxin FU ; Jing LI ; Huaqing TAN ; Yingqi XU ; Yanan MA ; Wei WANG ; Jia WANG ; Haipeng CHEN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Liqun WU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):223-230
ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza, and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter, prospective, non-randomized, parallel, controlled trial was conducted from October 2021 to May 2022 in five hospitals, including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness (ILI) cases were collected, and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention, they were assigned to the observation group (108 cases) or the control group (108 cases). Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine (TCM) symptom score scale for influenza, influenza-related emergency (outpatient) visit rate, influenza hospitalization rate, and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled, with 108 in the observation group and 108 in the control group. Primary outcomes: (1) Incidence of ILI: The incidence was 12.0% (13/108) in the observation group and 23.1% (25/108) in the control group, with the observation group showing a significantly lower incidence (χ2=4.6, P<0.05). (2) Influenza confirmation rate: 3.7% (4/108) in the observation group and 4.6% (5/108) in the control group, with no statistically significant difference. Secondary outcomes: (1) TCM symptom score scale: after onset, nasal congestion and runny nose scores differed significantly between the two groups (P<0.05), while other symptoms such as fever, sore throat, and cough showed no significant differences. (2) Influenza-related emergency (outpatient) visit rate: 84.6% (11 cases) in the observation group and 96.0% (24 cases) in the control group, with no significant difference. (3) Time to onset after exposure: The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group, with a statistically significant difference (P<0.05). ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions, Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.
3.Clinical Efficacy of Xiaoji Hufei Formula in Protecting Children with Close Contact Exposure to Influenza: A Multicenter,Prospective, Non-randomized, Parallel, Controlled Trial
Jing WANG ; Jianping LIU ; Tiegang LIU ; Hong WANG ; Yingxin FU ; Jing LI ; Huaqing TAN ; Yingqi XU ; Yanan MA ; Wei WANG ; Jia WANG ; Haipeng CHEN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Liqun WU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):223-230
ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza, and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter, prospective, non-randomized, parallel, controlled trial was conducted from October 2021 to May 2022 in five hospitals, including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness (ILI) cases were collected, and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention, they were assigned to the observation group (108 cases) or the control group (108 cases). Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine (TCM) symptom score scale for influenza, influenza-related emergency (outpatient) visit rate, influenza hospitalization rate, and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled, with 108 in the observation group and 108 in the control group. Primary outcomes: (1) Incidence of ILI: The incidence was 12.0% (13/108) in the observation group and 23.1% (25/108) in the control group, with the observation group showing a significantly lower incidence (χ2=4.6, P<0.05). (2) Influenza confirmation rate: 3.7% (4/108) in the observation group and 4.6% (5/108) in the control group, with no statistically significant difference. Secondary outcomes: (1) TCM symptom score scale: after onset, nasal congestion and runny nose scores differed significantly between the two groups (P<0.05), while other symptoms such as fever, sore throat, and cough showed no significant differences. (2) Influenza-related emergency (outpatient) visit rate: 84.6% (11 cases) in the observation group and 96.0% (24 cases) in the control group, with no significant difference. (3) Time to onset after exposure: The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group, with a statistically significant difference (P<0.05). ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions, Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.
4.Utility of the China-PAR Score in predicting secondary events among patients undergoing percutaneous coronary intervention.
Jianxin LI ; Xueyan ZHAO ; Jingjing XU ; Pei ZHU ; Ying SONG ; Yan CHEN ; Lin JIANG ; Lijian GAO ; Lei SONG ; Yuejin YANG ; Runlin GAO ; Xiangfeng LU ; Jinqing YUAN
Chinese Medical Journal 2025;138(5):598-600
5.Observation on the Curative Effect of Lishui Xiaozhong Granules Combined with Conbercept in Treating Diabetic Macular Edema
Xueyan YANG ; Lijun LAN ; Shengguang WU ; Hai ZHU ; Jue ZHANG
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(5):1133-1139
Objective To investigate the efficacy of Lishui Xiaozhong Granules combined with Conbercept for the treatment of diabetic macular edema(DME).Methods From December 2022 to June 2023,46 patients(46 eyes)with DME of spleen and kidney yang deficiency complicated with blood-stasis obstructing the eye collaterals syndrome admitted to Foshan Hospital of Traditional Chinese Medicine were selected as the study objects.According to the principle of single-blind randomized controlled trial,the patients were randomly divided into treatment group and control group by random number table method,with 23 cases(23 eyes)in each group.The control group was treated with intravitreal injection of Conbercept,and the treatment group was treated with oral use of Lishui Xiaozhong Granules on the basis of treatment for the control group.The course of treatment lasted 3 months and then a follow-up for 6 months was conducted.Before and after treatment,the two groups were observed int the changes of traditional Chinese medicine(TCM)syndrome score,best corrected visual acuity(BCVA,LogMAR),central macular thickness(CMT),mean vessel density(VD)of superficial capillary plexus(SCP)and deep capillary plexus(DCP)in macular area,and the amplitude density and the latency of P1 and N1 wave in the R1 ring of multifocal electroretinogram(mf-ERG).Results(1)After 1,3 and 6 month(s)of treatment,BVCA in the two groups was improved when compared with that at the previous observation time point(P<0.05),and the improvement in the treatment group was superior to that in the control group after 1,3 and 6 month(s)of treatment(P<0.01).(2)After 1,3 and 6 month(s)of treatment,the CMT of the two groups was lowered as compared with that at the previous observation time point(P<0.05),and the decrease in the treatment group was significantly superior to that in the control group(P<0.01).(3)After 6 months of treatment,SCP-VD and DCP-VD in the two groups showed no obvious changes when compared with those before treatment(P>0.05),the differences between the two groups after treatment were no statistically significant,either(P>0.05).(4)After 1,3 and 6 month(s)of treatment,the amplitude densities of P1 wave and N1 wave in the R1 ring of mf-ERG in the two groups were increased when compared with those at the previous observation time point(P<0.05),and the latency of P1 wave and N1 wave was shortened when compared with that at the previous observation time point(P<0.05),and the treatment group had stronger effect on increasing the amplitude densities and on shortening the latency than the control group(P<0.01).(5)After 6 months of treatment,the scores of TCM syndromes in the treatment group were lowered(P<0.05)while the scores in the control group showed no obvious changes as compared with those before treatment.The intergroup comparison showed that the decrease of TCM syndrome score in the treatment group was significantly superior to that in the control group(P<0.01).Conclusion In the treatment of DME with spleen and kidney yang deficiency complicated with blood-stasis obstructing the eye collaterals syndrome,Lishui Xiaozhong Granules combined with Conbercept have no influence on improving the SCP-VD and DCP-VD,but the combined therapy exerts satisfactory efficacy on increasing BCVA and on improving macular oedema,retinal function in the macular area and systemic symptoms.
6.The influence of enriched environment on cognitive impairment and GAP-43 content changes in pregnant mice with obstructive sleep apnea-hypopnea syndrome through regulating the NF-κB/NLRP3 pathway
Yunzhou Cheng ; Xueyan Li ; Yueming Zhang ; Rumeng Wei ; Yang Wang
Acta Universitatis Medicinalis Anhui 2025;60(7):1212-1217
Objective :
To investigate the effect of environmental enrichment on cognitive impairment and hippo- campus GAP-43 changes induced by exposure to obstructive sleep apnea-hypopnea syndrome ( OSAHS) during the period of late pregnancy in mice,and to explore relative inflammatory pathway mechanism.
Methods :
The experi- mental group of C57BL/6J pregnant mice were exposed to an intermittent hypoxic environment for 7 consecutive days starting from gestational day 15.The corresponding offspring were then placed in an enriched environment from postnatal day 21 to 2 months of age (designated as OSAHS + EE group) or in a normal environment (designat- ed as OSAHS group) .Pregnant mice in the control group were maintained in a normal oxygen environment,and their corresponding offspring were placed in an enriched environment (designated as Control + EE group) or a nor- mal environment (designated as Control group) at the same ages.The spatial learning and memory ability of the mice was assessed by Morris water maze at the age of 2 months.The mRNA levels of NF-kB,NLRP3 and GAP-43 in the hippocampus were detected by real-time fluorescence quantitative PCR , and the protein levels of NLRP3 and GAP-43 in the hippocampus were detected by Western blot.
Results:
Compared with Control group,the swimming distance increased (P<0. 01) ,and the percentage of swimming distance in target quadrant decreased (P<0. 01) in OSAHS group.The level of NF - κB mRNA,NLRP3 mRNA and protein in the hippocampus was increased,and the level of GAP-43 mRNA and protein was decreased (P<0. 01) .Compared with the Control group,there were no significant differences in swimming distance,percentage of swimming distance,NF-κB mRNA,NLRP3 mRNA and protein content in the OSAHS + EE group.
Conclusion
OSAHS during pregnancy impairs the learning and memory ability of offspring mice and reduces the level of GAP-43 protein.The mechanism may be related to the in- crease of NF-κB / NLRP3 level,and environmental enrichment can improve the damage.
7.Study on Quality Markers of Saorilao Qingfei Zhike Capsules Based on UPLC-QTOF-MS and Network Pharmacology Technology
Zhaozuo ZOU ; Tongqiang SHANGGUAN ; Huajie YANG ; Yingying LUO ; Shang LYU ; Shuangling YANG ; Xueyan LI ; Yuying LUO ; Yi RAO
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(1):103-114
Objective Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)and network pharmacology technology combined with pharmacodynamic experiments were used to analyze the quality markers(Q-markers)in Saorilao Qingfei Zhike Capsules.Methods Using UPLC-Q-TOF-MS technology,the chemical components in different polar extracts of Saorilao Qingfei Zhike Capsules was analyzed.Potential pharmacological components were screened by using antitussive and expectorant models.The"components-targets-diseases"network was constructed and potential Q-markers were screened by network pharmacology technology.Then we conducted pharmacodynamic validation to confirm the Q-markers,which have antitussive and expectorant effects in Saorilao Qingfei Zhike Capsules.Results A total of 120 compounds were obtained from the Saorilao Qingfei Zhike Capsules through qualitative analysis.Among the extracts of different polarity,44 compounds were derived from petroleum ether extract,85 compounds were derived from ethyl acetate extract,79 compounds were derived from n-butanol extract,and 71 compounds were derived from water extract.The results of pharmacological experiments showed that among extracts of different polarity,petroleum ether extract had the best antitussive effect,while n-butanol extract had the best expectorant effect.Three core components for eliminating phlegm and relieving cough were screened through network pharmacology techniques:farcalinol,farcalinediol,and rubimaillin.Pharmacodynamic studies verified that all core components mentioned above have certain antitussive and expectorant effects.Conclusion Based on the above research,farcalinol,farcalindiol,and rubimaillin can be used as Q-markers for the antitussive and expectorant effects of Saorilao Qingfei Zhike Capsules.This paper provides reference for the quality standard of Saorilao Qingfei Zhike Capsules.
8.Stiff left atrial syndrome after Mei mini maze procedure for atrial fibrillation: A retrospective study
Qi YANG ; Shiao DING ; Xueyan JIANG ; Yuan YUAN ; Hao LIU ; Ju MEI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(03):434-438
Objective To analyze the clinical characteristics of stiff left atrial syndrome (SLAS) after Mei mini maze procedure for atrial fibrillation (AF), and to explore its risk factors and treatments. Methods We retrospectively analyzed the clinical data of the patients who underwent Mei mini maze procedure in Xinhua Hospital between 2010 and 2020. According to whether SLAS occurred in the early postoperative period, patients were divided into a SLAS group and a non-SLAS group. The basic data, perioperative echocardiogram and laboratory test indexes of the two groups were compared. Results A total of 1 056 patients were collected. There were 672 (63.6%) males with an average age of 63.6±9.3 years, including 489 patients with persistent AF and 567 patients with paroxysmal AF. Fourteen (14/1 056, 1.3%) patients developed SLAS, with an average occurrence time of 2.1±1.1 days after the surgery. The average follow-up time of the whole group was 21.4±7.8 months. Two patients in the SLAS group developed SLAS again after discharge, and the occurrence time was 3 weeks and 4 weeks after the operation, respectively; while no SLAS occurred after discharge in the non-SLAS group. Diabetes and small preoperative left atrial diameter were risk factors for SLAS after surgery. Patients with SLAS had a good prognosis after adequate diuretic therapy. Conclusion The incidence of SLAS after Mei mini maze procedure for AF is low, and it mostly occurs in the early postoperative period. After adequate diuretic treatment, the prognosis is good.
9.Analysis on Components Absorbed into Blood and Cerebrospinal Fluid of Schisandrae Chinensis Fructus Based on Sequential Metabolism
Shuang YU ; Yanli PAN ; Huining LIU ; Xueyan LI ; Xinyu WANG ; Dongying QI ; Fulu PAN ; Qianqian WANG ; Xiaoyu CHAI ; Guopeng WANG ; Tao MA ; Yang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):114-123
ObjectiveTo identify the prototypical components and metabolites absorbed into blood and cerebrospinal fluid of Schisandrae Chinensis Fructus(SCF) based on sequential metabolism combined with liquid chromatography-mass spectrometry. MethodBlood and cerebrospinal fluid samples of integrated metabolism, intestinal metabolism and hepatic metabolism were collected from male SD rats after gavage and in situ intestinal perfusion administration, and ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC Q-Exactive Orbitrap MS) was used to analyze and compare the differences in the spectra of SCF extract, blank plasma, administered plasma, blank cerebrospinal fluid and administered cerebrospinal fluid with ACQUITY UPLC BEH Shield RP18 column(2.1 mm×100 mm, 1.7 µm), the mobile phase was acetonitrile(A)-0.1% formic acid aqueous solution(B) for gradient elution(0-7 min, 95%B; 7-12 min, 95%-35%B; 12-17 min, 35%-15%B; 17-20 min, 15%-12%B; 20-22 min, 12%-5%B; 22-23 min, 5%B; 23-25 min, 5%-95%B; 25-28 min, 95%B). And heated electrospray ionization(HESI) was used with positive and negative ion modes, the scanning range was m/z 100-1 500. The prototypical constituents and their metabolites absorbed into blood and cerebrospinal fluid of SCF were identified according to the retention time, characteristic fragments, molecular formulae and the information of reference substances. ResultA total of 42 chemical components were identified in the extract of SCF, including lignans, flavonoids, amino acids, tannins, and others, of which lignans were the main ones. A total of 27 prototypical components and 14 metabolites were identified in plasma samples from different sites. A total of 15 prototypical components and 9 metabolites were identified in cerebrospinal fluid. The main metabolic reactions involved in the formation of metabolites were mainly demethylation, methylation, demethoxylation and hydroxylation. ConclusionThrough the systematic identification of the prototypical components and metabolites of SCF in rats, it provides data support for further better exploring the material basis of SCF in the treatment of central nervous system diseases.
10.Analysis of Inhibitory Effect of Berberine Compounds on Acetylcholinesterase and Blood-brain Barrier Permeability
Fulu PAN ; Yang LIU ; Huining LIU ; Shuang YU ; Xueyan LI ; Xinyu WANG ; Dongying QI ; Xiaoyu CHAI ; Qianqian WANG ; Zirong YI ; Yanli PAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):116-124
ObjectiveTo examine the inhibitory effects of berberine compounds, including columbamine, on acetylcholinesterase from the perspectives of drug-target binding affinity and kinetics and explore the blood-brain barrier (BBB) permeability of these compounds in different multi-component backgrounds. MethodThe median inhibitory concentration (IC50) of acetylcholinesterase by berberine compounds including columbamine was measured using the Ellman-modified spectrophotometric method. The binding kinetic parameters (Koff) of these compounds with acetylcholinesterase were determined using the enzyme activity recovery method. A qualitative analysis of the ability of these components to penetrate the BBB and arrive at the brain tissue in diverse multi-component backgrounds (including medicinal herbs and compound formulas) was conducted using ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). ResultBerberine compounds, including columbamine, exhibited strong inhibition of acetylcholinesterase, with IC50 values in the nanomolar range. Moreover, they displayed better drug-target binding kinetics characteristics (with smaller Koff values) than the positive control of donepezil hydrochloride (P<0.01), indicating a longer inhibition duration of acetylcholinesterase. Berberine components such as columbamine could penetrate the BBB to arrive at brain tissue in the form of a monomer, as well as in the multi-component backgrounds of Coptis and Phellodendri Chinensis Cortex medicinal extracts and the compound formula Huanglian Jiedutang. ConclusionThese berberine compounds such as columbamine exhibit a strong inhibitory effect on acetylcholinesterase and can arrive at brain tissue in multi-component backgrounds. In the level of pharmacological substance, this supports the clinical efficacy of compound Huanglian Jiedutang in improving Alzheimer's disease, providing data support for elucidating the pharmacological basis of compound Huanglian Jiedutang.


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