Six compounds were isolated from the ethyl acetate fraction of Citri Sarcodactylis Fructus by using various column chromatographic methods, such as MCI Gel CHP-20, ODS, Sephadex LH-20, silica gel and semipreparative HPLC. Their structures were identified to be citrusin G (1), citrusin H (2), citrusin E (3), syringin (4), coniferin (5), methylconiferin (6) by NMR, HR-ESI-MS, UV, IR spectra. Compounds 1 and 2 were new secondary metabolism products and 3-6 were obtained from the titled material for the first time. Compound 1 showed anti-renal fibrosis activity in TGF-β1-induced kidney proximal tubular cells.

Objective To explore the role and efficacy of VEGF and HGF gene adenovirus vector in promoting angiogenesis in ischemic tissue.Methods 84 Kunming mice were randomly divided into sham group,control group,VEGF group,HGF group and VEGF+HGF group,and the left lower limb ischemia model was established.The blood supply of ischemic tissue was observed by rheometer,and the expression levels of VEGF and HGF in each group were detected by Western Blot and ELISA.Immunohistochemical staining was used to detect angiogenesis(CD31,SMA)in ischemic tissues.Safety was assessed by side effects during treatment in mice.Results After the successful modeling,the blood flow velocity of the left lower limb in each group decreased significantly.On the 7th day after operation,the blood flow of the left lower limb in each group was significantly better than that on the 0th day after operation(P<0.05),and the blood flow of the left lower limb in Ad-VEGF-HGF group was significantly better than that in other groups(P<0.05).On the 28th day after operation,the blood flow of the left lower limb in Ad-VEGF-HGF group gradually stabilized,the blood flow in Ad-VEGF-HGF group was significantly better than that in other groups,and both VEGF group and HGF group were significantly better than the control group(P<0.05).On the 7th,14th,and 28th days following surgery,HGF and VEGF protein levels in the Ad-HGF,Ad-VEGF,and Ad-VEGF-HGF groups were substantially greater than those in the control group(P<0.05).The expression level in the Ad-VEGF-HGF group peaked on the 14th day(all P<0.001)and subsequently declined to preoperative levels on the 28th day after operation.Conclusion Ad-VEGF-HGF gene injection can effectively boost VEGF and HGF protein expression and rapidly reach the relative peak level,encour-aging angiogenesis after lower limb ischemia,increasing blood flow,and improving lower limb circulation.

An integrated evaluation model based on the combination of traditional trait identification and modern chemical analysis was used for the identification of key indexes of grade classification and the establishment of grade quality standard of Lycium barbarum fruits (LBF) from Ningxia genuine producing area. Under the guidance of herbal examination and market survey, particle size, skin color and imperfection were taken as the external trait indicators; focusing on the comprehensiveness and validity of the quality evaluation, 2-O-β-D-glucopyranosyl-L-ascorbic acid (AA-2βG), zeaxanthin dipalmitate (ZD) and volatile ether extractives were used as important parameters involving in quality evaluation in addition to the pharmacopoeia test items and determination indicators such as moisture, ash, water-soluble extractives, Lycium barbarum polysaccharide (LBP) and betaine. The quality differences between different traits and grades of LBF as well as the relevance between character and quality were further investigated by mathematical and statistical means such as t-test analysis, correlation analysis and principal component analysis (PCA). Furthermore, the activities of extractives from different grades of LBF were compared at cellular level. The results showed that LBF were mainly preferred for large and red ones; except for betaine, the other index components were relatively high (moisture and ash were low) in the first-grade and samples with bright-red skin color. Besides, there was a significant correlation between skin color and moisture, water-soluble extractives, LBP, AA-2βG and ZD contents. Considering the results of the study and the market situation, the present study took the grain size and skin color of LBF as the core of evaluation, and at the same time introduced the multi-indicator components including LBP, AA-2βG, ZD, water-soluble extractives and moisture to further guide the grading, and established the quality standard of LBF grades combining the trait indexes and the chemical composition. More importantly, in vitro cell models both preliminarily confirmed that the first-grade LBF played a more significant "nourishing liver and kidney" effect, which provided an experimental basis for the quality control of LBF and promoted the realization of high quality and good price.

Mitophagy, a highly precise form of autophagy, plays a pivotal role in maintaining cellular homeostasis by selectively targeting and eliminating damaged mitochondria through a process known as mitophagy. Within this tightly regulated mechanism, dysfunctional mitochondria are specifically delivered to lysosomes for degradation. Disruptions in mitophagy have been implicated in a diverse range of pathological conditions, spanning diseases of the nervous system, cardiovascular system, cancer, aging, and metabolic syndrome. The elucidation of mitophagy’s impact on cardiovascular disorders, liver diseases, metabolic syndromes, immune dysfunctions, inflammatory conditions, and cancer has significantly advanced our understanding of the complex pathogenesis underlying these conditions. These studies have shed light on the intricate connections between dysfunctional mitophagy and disease progression. Among the disorders associated with mitochondrial dysfunction, insulin resistance (IR) stands out as a prominent condition linked to metabolic disorders. IR is characterized by a diminished response to normal levels of insulin, necessitating higher insulin levels to trigger a typical physiological reaction. Hyperinsulinemia and metabolic disturbances often coexist with IR, primarily due to defects in insulin signal transduction. Oxidative stress, stemming from mitochondrial dysfunction, exerts dual effects in the context of IR. Initially, it disrupts insulin signaling pathways and subtly contributes to the development of IR. Additionally, by inducing mitochondrial damage and autophagy, oxidative stress indirectly impedes insulin signaling pathways. Consequently, mitophagy acts as a protective mechanism, encapsulating damaged or dysfunctional mitochondria through the autophagy-lysosome pathway. This efficient process eliminates excessive oxidative stress reactive. The intricate interplay between mitochondrial function, oxidative stress, mitophagy, and IR represents a captivating field of investigation in the realm of metabolic disorders. By unraveling the underlying complexities and comprehending the intricate relationships between these intertwined processes, researchers strive toward uncovering novel therapeutic strategies. With a particular focus on mitochondrial quality control and the maintenance of redox homeostasis, these interventions hold tremendous potential in mitigating IR and enhancing overall metabolic health. Emerging evidence from a myriad of studies has shed light on the active involvement of mitophagy in the pathogenesis of metabolic disorders. Notably, interventions such as exercise, drug therapies, and natural products have been documented to induce mitophagy, thereby exerting beneficial effects on metabolic health through the activation of diverse signaling pathways. Several pivotal signaling molecules, including AMPK, PINK1/Parkin, BNIP3/Nix, and FUNDC1, have been identified as key regulators of mitophagy and have been implicated in the favorable outcomes observed in metabolic disorders. Of particular interest is the unique role of PINK1/Parkin in mitophagy compared to other proteins involved in this process. PINK1/Parkin exerts influence on mitophagy through the ubiquitination of outer mitochondrial membrane proteins. Conversely, BNIP3/Nix and FUNDC1 modulate mitophagy through their interaction with LC3, while also displaying certain interrelationships with each other. In this comprehensive review, our objective is to investigate the intricate interplay between mitophagy and IR, elucidating the relevant signaling pathways and exploring the treatment strategies that have garnered attention in recent years. By assimilating and integrating these findings, we aim to establish a comprehensive understanding of the multifaceted roles and intricate mechanisms by which mitophagy influences IR. This endeavor, in turn, seeks to provide novel insights and serve as a catalyst for further research in the pursuit of innovative treatments targeting IR.

Objective To explore the effect of Shugan Lipi decoction on inflammation and intestinal flora,Toll like receptor 4(TLR4),T cell immunoglobulin domain and mucin domain-3(Tim-3)in non-alcoholic steatohepatitis(NASH)rats.Methods The NASH model was established by feeding methionine and choline deficient diet for 4 weeks.SD rats were randomly divided into blank group(intragastric administration with 0.9％NaCl),model group(NASH model,intragastric administration with 0.9％NaCl),and experimental group(NASH model,intragastric administration with 6.18g·kg-1 Shugan Lipi decoction).Illumina sequencing by synthesis method was used to detect the 16S rRNA sequence of rat Intestinal microbiota.Western blot method was used to detect the expression levels of Tim-3 and TLR4 proteins.Enzyme-linked immunosorbent assay was used to detect tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-10 levels in each group of rats.Results After 4 weeks of medication,the relative abundance of Bacteroidetes in the blank,model and experimental groups were(47.96±10.52)％,(42.90±15.01)％and(57.15±10.99)％;the relative abundance of Firmicutes were(49.27±9.99)％,(53.06±11.47)％and(39.99±11.88)％;the relative expression levels of Tim-3 protein were 1.03±0.07,0.24±0.06 and 1.57±0.11;the relative expression levels of TLR4 protein were 1.04±0.11,3.23±0.33 and 0.94±0.27;the levels of TNF-α were(403.03±25.25),(576.87±60.29)and(385.16±37.67)pg·mL-1;the levels of IL-6 were(125.35±14.07),(189.75±34.30)and(113.71±18.35)pg·mL-1;the levels of IL-10 were(123.20±15.96),(66.71±11.94)and(119.54±10.57)pg·mL-1,respectively.The above indexes in the experimental group showed statistically significant differences compared with the model group(P＜0.01,P＜0.05).Conclusion Shugan Lipi decoction may regulate inflammatory cytokines by affecting intestinal flora and TLR4,Tim-3 protein expression,affect liver inflammatory response,and improve NASH.

Objective:To investigate the interaction of platelet factor 4(PF4)with tumor necrosis factor-α(TNF-α)in the pathoge-nesis of chronic periodontitis(Ⅲ-C).Methods:22 patients with chronic periodontitis(Ⅲ-C)and 22 subjects with periodontal health were recruited.Before and after periodontal treatment,the concentration of PF4 and TNF-α in gingival crevicular fluid(GCF)and ser-um,the amount of PF4 released by platelets after lipopolysaccharide(LPS)stimulated peripheral blood platelets were measured by ELISA.Flow cytometry was used to calculate the number of platelets in GCF before and after treatment.Results:The concentrations of PF4 and TNF-α in the GCF and serum of the patients were higher than those in the periodontal healthy group(P＜0.05).After treat-ment,the concentrations of PF4 and TNF-α in the GCF were significantly lower than those before treatment(P＜0.05),and the con-centrations of PF4 and TNF-α in the serum were unchanged(P＞0.05).After LPS stimulation of the platelets in blood before and after treatment,the concentration of PF4 released by the platelets was much higher in the patients than that in the healthy controls(P＜0.01),and the concentration was significantly lower after periodontal treatment than before treatment(P＜0.01).The number of CD41/CD61 double positive platelets and CD45 negative cells in GCF before periodontal treatment were 85 times and 87 times higher than those in periodontal healthy subjects,respectively(P＜0.01).Conclusion:PF4 and TNF-α have synergistic effect in the patho-genesis of chronic periodontitis.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Brucellosis,a worldwide epidemic bacterial zoonotic infectious disease caused by bacteria of the genus Brucella,jeopardizes livestock production and poses a major threat to public health safety.Among the various components of Brucella,the outer membrane proteins play crucial roles as the primary immune and protective antigens.These proteins are closely asso-ciated with Brucella's virulence,regulation of the immune response,and ability to survive and multiply within host cells.This article summarizes recent research progress in the primary outer membrane proteins of Brucella,and offers a synthesized view of the current knowledge landscape.Understanding the antigenic characteristics of Brucella outer membrane proteins may sub-stantially contribute to the establishment of new diagnostic methods and the design of new vaccines,thus potentially leading to more effective prevention strategies against brucellosis.The review provides a reference for future studies and may aid in brucel-losis control efforts.

Immunotherapy is an important breakthrough in canc-er treatment.Unfortunately,low drug concentration in tumor sites almost ineffectively initiates immune responses and thereby severely limits immune therapy applications in clinics.Nanoma-terials are well-recognized drug delivery system in cancer thera-py.Nanographene oxide(NGO)have shown immense perti-nence for anti-cancer drug delivery owing to their ultra-high sur-face area,chemical stability,good biocompatibility and excel-lent photosensitivity.In addition,functionalized modifications on the surface of NGO increase tumor targeting and minimize cy-totoxicity.This study focuses on reviewing the literature and up-dates on NGO in drug delivery and discussing the possibilities and challenges of NGO in cancer synergetic therapy.

Objective:To explore the clinicopathological characteristics and the related influencing factors of efficacy and prognosis of elderly patients with malignant mesothelioma(MM)in Chinese population.Methods:We retrospectively analyzed the clinical data of 115 patients aged 65 years and above who were diagnosed with MM in Beijing Hospital, Peking University Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences between November 2007 and July 2024, and the patients were grouped according to age(≥75 years in the older group and <75 years in the younger group), histological types and therapy regimens.Kaplan-Meier curve and Log-rank test were performed.Cox regression was used in prognostic analysis.Results:The positive expression rate of Calretinin in the Chinese elderly population with MM was consistent with previous reports, while the positive rates of Cytokeratin 5/6(CK5/6), WT-1, and D2-40 were much lower.The overall response ratio(ORR)for first-line treatment was 17.3%(9/52), and the disease control rate(DCR)was 92.3%(48/52).The ORR for second-line treatment was 7.7%(1/13)and the DCR was 76.9%(10/13).The ORR and DCR were higher in the first-line immunotherapy group than in the chemotherapy group, 50.0% vs.14.6%( P=0.134)and 100.0% vs.91.6%( P=1.000), respectively.The ORR in the second-line immunotherapy group was higher than that in the chemotherapy group, 25.0% vs.0, respectively, and the DCR were both 75.0% in two groups.The median progression free survival(mPFS)was 9.2 months and median overall survival(mOS)was 19.0 months for patients receiving first-line treatment, and the mPFS was 3.3 months and mOS was 11.0 months for second-line therapy.The first-line immunotherapy provided more shorter mPFS(1.6 months vs.9.2 months, P=0.081)and longer mOS(not reached vs.18.1 months, P=0.147)than the chemotherapy group.The younger group had prolonged mPFS(9.7 months vs.7.2 months, P=0.305)while shorter mOS(18.1 months vs.23.9 months, P=0.289)compared with the older group, and none of them reached statistical differences.Both mPFS and mOS were prolonged in the epithelioid subtype compared with the non-epithelioid subtypes, 10.4 months vs.1.6 months( P<0.001)and 20.3 months vs.4.6 months( P=0.803), respectively.Both mPFS(7.1 months vs.4.7 months, P=0.583)and mOS(18.3 months vs.6.3 months, P=0.134)were prolonged in the second-line chemotherapy group compared with the immunotherapy group.The Cox regression analysis showed that gender, Eastern Cooperative Oncology Group, Performance Status(ECOG PS)and positive CK5/6 were both the independent predictors for the first-line PFS.Histological type was an independent prognostic factor for the first-line OS. Conclusions:MM in the Chinese elderly population exhibits unique clinicopathologic characteristics.The immunotherapy improves ORR, DCR and prolongs mOS in first-line use, and improves ORR in second-line.First-line treatment improves mPFS in the younger group compared with the older group.Multivariate Cox regression demonstrates that gender, ECOG PS and CK5/6 expression are both predictors of efficacy, and histological type is an independent prognostic factor for survival of the Chinese elderly population with MM.