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.

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.

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.

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.

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．

Objective To explore the protective effect and underlying mechanism of roxadustat(FG-4592),hypoxia-inducible factor-α(HIF-α)prolyl hydroxylase inhibitor,on brain injury caused by heat stroke(HS).Methods A total of 140 male C57BL/6J mice(6～8 weeks old,weighing 18～22 g)were subjected,and 40 of them were randomly divided into HS group,and low-,medium-and high-dose roxadustat groups(LD,MD and HD groups,5,10 and 20 mg/kg),with 10 mice in each group.The 24-hour survival rate was observed to determine the optimal dosage of roxadustat after modeling.Additionally,the remaining 100mice were randomly allocated to normal control(Control)group,roxadustat(FG-4592)group,HS group,and roxadustat+HS(FG-4592+HS)group,with 25 mice in each.Heat shock was inflicted to establish mouse model of HS.Modified neurological severity score(mNSS)was used to assess neurological function.HE staining of brain sections was performed to examine pathological damage,and Fluoro-Jade C staining was applied to observe neuronal degeneration.The activity of total superoxide dismutase(SOD)and content of malondialdehyde(MDA)in brain tissue were measured to assess oxidative stress.Transmission electron microscopy was employed to visualize mitochondrial damage.Western blotting was performed to assess the protein levels of Caspase-3,Cleaved Caspase-3,Mfn1,Mfn2,Opa1,Fis1,HIF-1α,HO-1 and p-Drp1(Ser616)/Drp1 ratio in the cerebral cortex.Results Compared to the HS group,FG-4592 significantly improved the survival rate of HS mice within 24 h,with the MD group showing the highest survival rate.Compared to the Control group,the HS group showed an increase in mNSS score(P＜0.05),an elevation in the MDA content in the cerebral cortex(P＜0.05),and a decrease in total SOD activity in the cerebral cortex(P＜0.05);HE staining revealed pathological damage in the cerebral cortex,and Fluoro-Jade C staining displayed obvious neuronal degeneration in the cerebral cortex;Electron microscopy revealed obvious mitochondrial structural damage in the cerebral cortex tissue;The protein expression of Caspase-3,Cleaved Caspase-3,Fis1,HIF-1α,HO-1 and p-Drp1(Ser616)/Drp1 ratio was increased(P＜0.05),while that of Mfn1,Mfn2,and Opa1 was decreased(P＜0.05).Pretreatment with FG-4592 significantly reduced the mNSS score in HS mice(P＜0.05),decreased MDA content(P＜0.05),and enhanced total SOD activity(P＜0.05).Additionally,FG-4592 pretreatment improved pathological damage in the cerebral cortex,reduced neuronal degeneration,and mitigated mitochondrial structural damage.Furthermore,it decreased the protein levels of Caspase-3,Cleaved Caspase-3,Fis1 and p-Drp1(Ser616)/Drp1 ratio(P＜0.05),while increased the levels of Mfn1,Mfn2,Opa1,HIF-1α,and HO-1(P＜0.05).Conclusion Roxadustat regulates the balance between mitochondrial fission and fusion,reduces mitochondrial structural damage,oxidative stress and apoptosis,and alleviates heat stroke-induced brain injury.

Objective:To analyze long-term prognosis and influencing factors of recurrence in vocal fold leukoplakia treated by endoscopic cordectomy with CO 2 laser. Methods:A retrospective review was conducted on 599 patients with vocal fold leukoplakia [566 males and 33 females, aged 17-84 years (median age 55 years)], undergoing endoscopic cordectomy by CO 2 laser under general anesthesia at the Department of Otorhinolaryngology Head and Neck Surgery of Beijing Tongren Hospital, Capital Medical University, from January 2000 to December 2023. The study analyzed the clinical features, pathological grade, surgical methods, postoperative voice function, recurrence, malignant changes and analyzed the long-term efficacy and and its influencing factors. The patients were followed up for a duration of 6-249 months postoperatively, with a median follow-up time of 48 months. SPSS 20.0 software was used for statistical analysis. Results:Among the 599 patients, the histopathological grades included simple squamous cell hyperplasia in ( n=264, 44.08%), mild dysplasia ( n=96, 16.03%), moderate dysplasia ( n=74, 12.35%), severe dysplasia( n=43, 7.81%), carcinoma in situ( n=35, 5.84%), and carcinoma in situ with microinvasion( n=87, 14.52%). The 3-year and 5-year overall recurrence rates were 12.91% and 16.00%, respectively. In patients with precancerous lesion, 3.91% of recurrences presented with an upgraded pathologic grade and 2.34% evolved into carcinoma. The risk of recurrence was higher in lesions involving the anterior commissure, larger lesions, significant reduction/absence of mucosal waves, neovascularization/suspected neovascularization, and pathology of dysplasia/carcinoma in situ/carcinoma in situ with microinvasion( F=44.76,21.54,11.55,8.78,23.20,respectively, P<0.05). Additionally, patients with recurrent disease exhibited higher reflux symptom index scores compared to those without recurrence. Exophytic lesion characteristics and the inability to cease smoking postoperatively were identified as independent risk factors for recurrence with an upgraded pathological grade, with odds ratios of 8.675 and 11.380 times greater than those with non-exophytic lesions and successful smoking cessation, respectively. At the 6-months postoperative assessment, patients who underwent subepithelial cordectomy (typeⅠ) demonstrated a statistically significant increase in fundamental frequency ( t=-3.38, P<0.05), and while other voice acoustic parameters were not significantly different.Conversely, those who underwent transmuscular cordectomy (TypeⅢ) exhibited significant alterations in multiple voice acoustic parameters when compared to preoperative values ( P<0.05). Furthermore, postoperative vocal fold adhesions developed in 84 patients with 13 of these individuals requiring surgical intervention for adhesion release. Conclusions:Lesions involving the anterior commissure, larger lesions, pathology of dysplasia/carcinoma in situ/carcinoma in situ with microinfiltration, significant reduction/absence of vocal fold mucosal waves, and neovascularization visible under NBI are indicative of an increased risk of recurrence, whereas exophytic lesions and the inability to cease smoking postoperatively significantly increase the risk of recurrence with elevated pathologic grade. Recovery of postoperative voice quality is procedure-dependent, underscoring the importance of surgical approach selection in the management of vocal fold leukoplakia.

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.

Objectives:To establish a comprehensive system of Cardiovascular Academic Performance Evaluation(CAPE)and rank global TOP100 medical institutions in the fields of cardiovascular diseases(CVD). Methods:CVD-related terms were extracted from Medical Subject Headings(MeSH),Embase thesaurus(EMtrees)and International Classification of Diseases(ICD)by CVD-related professionals,as well as by librarians and information professionals.Terminology databases(named as Fuwai Subject Headings)were established,and nine sub-disciplines were proposed,including ischemic heart diseases,hypertension,vascular diseases,arrhythmia,pulmonary vascular diseases,heart failure,congenital heart diseases,cardiomyopathy,and valvular heart diseases.The mapping patterns of sub-discipline,cardiovascular terminology and entry terms were pre-defined.The CVD-related research literature published from January 1,2016 to December 31,2022 were retrieved from Web of Science,PubMed and Scopus.Based on this,metadata were fused and duplicates were excluded.Fuwai Subject Headings were searched and matched into four respects for each literature,including subject words,titles,keywords,and abstracts,which was used to generate an information table of"Position—CVD terminology—Frequency",and to calculate CVD correlation scores and sub-discipline scores.We standardized the names of medical institutions and scholars,and make a ranking system for CAPE based on original articles with strong cardiovascular correlation(correlation score≥4).When evaluating the science and technological performance for Chinese hospitals in cardiovascular diseases,National Natural Science Foundation Projects,authorized invention patents,prize achievements,research platforms,and registered data of drug clinical trials in Center for Drug Evaluation(CDE)were considered besides research papers. Results:During 2016 and 2022,1 545 103 CVD research literatures were found worldwide.After excluding meeting abstracts,books,biographies,news,videos,audio texts,retracted publications,and corrections,1 178 019 CVD research literatures were further evaluated.518 058 literatures were indexed as"strongly correlated to CVD"using Fuwai Subject Headings.Besides papers,other data sources were also collected,including 11 143 CVD-related Natural Science Foundation Projects,19 382 CVD-related effective authorized invention patents,103 CVD-related national prize achievements,24 CVD-related national research platforms,and 2 084 CDE registered data of CVD-related drug clinical trials.Research teams from nine sub-disciplines reviewed and validated research literature in respective fields,and classification rules of corresponding sub-disciplines were created and improved based on their opinions.Finally,eleven individual indexes were chosen to construct CAPE system for ranking global TOP100 medical institutions in overall CVD field and TOP30 in nine sub-disciplines.From 2016 to 2022,the number of cardiovascular disease research papers published by Chinese institutes has increased by 123.5%,with a total of approximately 76.8 thousands papers published(about 30 papers per day on average),ranked the second under the United States(approximately 114.1 thousands papers).However,the proportion of papers published by the Chinese Journal Citation Reports(JCR)and the Chinese Academy of Sciences only ranked eighth in the world.In the comprehensive academic performance of original cardiovascular research papers in global hospitals from 2020 to 2022,only two Chinese medical institutions ranked in the TOP20 as evaluated by CAPE system. Conclusions:Based on multi-source data from 2016 to 2022,CAPE initiated to establish a cardiovascular academic performance evaluation system.