OBJECTIVE To establish HPLC fingerprint of Shuangdong capsules， and to study the spectral effect relationship of its anti-inflammatory effect. METHODS The fingerprints of 15 batches of Shuangdong capsules were established by HPLC，and the similarity evaluation was carried out； the foot swelling model was established to investigate the anti-inflammatory activity of Shuangdong capsules. The gray correlation analysis method was used to construct the spectral effect relationship for the anti- inflammatory effect of Shuangdong capsules using the swelling rate of rat foot and the levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， prostaglandin E2 （PGE2）， interleukin-6 （IL-6）， IL-8， IL-1β and tumor necrosis factor-α （TNF-α） in right hindfoot tissues as the pharmacodynamic indexes of anti-inflammatory effects. RESULTS Overall 15 batches of Shuangdong capsules identified 20 common peaks， the similarities were all greater than 0.97， and a total of 8 chromatographic peaks were identified. According to the gray correlation analysis， the correlation degrees between the peak area and the foot swelling rate and the levels of MDA， SOD， PGE2， IL-6， IL-8， IL-1β and TNF-α in 15 batches of Shuangdong capsules were 0.621 1- 0.783 5， 0.564 3-0.827 9， 0.581 0-0.845 3， 0.564 9-0.855 0， 0.583 1-0.856 4， 0.576 5-0.863 5， 0.564 1-0.838 0 and 0.572 5- 0.851 3， respectively. Among them， the chemical components represented by peak 4 （geniposidic acid）， peak 10 （chlorogenic acid） and the chemical composition represented by peak 2 were strongly correlated with anti-inflammatory efficacy indicators. CONCLUSIONS In this study， HPLC fingerprints of 15 batches of Shuangdong capsules were successfully established. Among them， geniposidic acid， chlorogenic acid may be its anti-inflammatory ingredients.

Objective To observe the clinical efficacy and safety of low dose dexmedetomidine for postoperative stability in patients with intracranial aneurysm during anesthesia induction.Method Patients with intracranial aneurysms treated with intracranial aneurysm clipping+intracranial pressure probe implantation were divided into treatment group and control group by cohort method.The patients in the control group were given intravenous midazolam injection 0.1 mg·kg-1 and cisatracurium 0.15 mg·kg-1 before the start of anesthesia induction to complete the anesthesia induction,and the endotracheal tube was inserted to observe the patient's breathing.Patients in the treatment group were given intravenous infusion of dexmedetomidine hydrochloride injection 0.4 μg·kg-1·h-1 from 15 min before anesthesia induction to the end of surgery;and the other drugs were the same as those in the control group.The hemodynamic indexes,sedation quality and recovery score,intracranial pressure waveform parameters were compared between the two groups before anesthesia induction(T1),immediately after anesthesia induction(T2),at tracheal intubation(T3),at aneurysm clipping(T4),at the end of operation(T5)and 2 min after extubation(T6),and the safety was evaluated.Results The control group and the treatment group were enrolled in 40 patients.The heart rate(HR)at T6 in the treatment group and the control group were(82.31±9.73)and(86.91±10.36)beat·min-1,respectively;the sedation-agitation scale(SAS)were 3.22±0.75 and 3.58±0.80,respectively;the mean waveform amplitude(MWA)on the first day after operation were(3.42±0.75)and(3.76±0.69)mmHg,respectively;the MWA on the second day after operation were(2.68±0.63)and(2.98±0.57)mmHg,respectively;the relationship of amplitude and pressure(RAP)on the first day after operation were 0.46±0.11 and 0.52±0.12,respectively.The above indexes in the treatment group were significantly different from those in the control group(all P＜0.05).There was no significant difference in Ramsay sedation score(Ramsay),anesthesia recovery time and visual analogue scale(VAS)score at 6 h after operation between the treatment group and the control group(all P＞0.05).The total incidence of adverse drug reactions during the wake-up period in the treatment group and the control group was 25.00％(10 cases/40 cases)and 36.84％(14 cases/38 cases),respectively,with no statistically significant difference(P＞0.05).Conclusion The application of low-dose dexmedetomidine hydrochloride injection in the induction period of anesthesia can stabilize the intracranial pressure waveform parameters,blood pressure,heart rate,respiratory rate,etc.after intracranial aneurysm surgery.

3ʹ-Hydroxy-4ʹ-methoxy-2-hydroxy-5-bromochalcone (hereinafter referred to as C13) is a novel chalcone derivative obtained in the process of structural modification of DHMMF, the antitumor active compound of Resina Draconis, in our laboratory. In this study, we investigated the effects of C13 on the proliferation and apoptosis of human gastric cancer HGC-27 and AGS cells and its potential mechanism of action. Firstly, through methyl thiazolyl tetrazolium (MTT), colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) staining, we found that C13 inhibited the proliferation ability of human gastric cancer HGC-27 and AGS cells. Using flow cytometry and Western blot, it was found that C13 induced apoptosis in human gastric cancer HGC-27 and AGS cells, and up-regulated the protein level of cleaved poly ADP-ribose polymerase (cleaved-PARP). The results of RNA sequencing analysis showed that the Erb-b2 receptor tyrosine kinase 4/phosphoinositide 3-kinases/AKT (ErbB4/PI3K/AKT) signaling pathway may be involved in anti-gastric cancer activity of C13. Finally, the results of immunoblotting assay showed that C13 treatment down-regulated the protein levels of ErbB4 and phospho-ErbB4, as well as down-regulated the phosphorylation levels of PI3K and AKT in human gastric cancer HGC-27 and AGS cells, which verified the results from RNA-seq analysis. In conclusion, C13 inhibited the proliferation and induced apoptosis of human gastric cancer cells, which may be related to the down-regulation of ErbB4/PI3K/AKT signaling pathway. This study may provide a candidate drug for the treatment of gastric cancer.

Objective:To explore the mechanism of hypertension inducing erectile dysfunction(ED)using transcriptomics and network pharmacology.Methods:We randomly divided 12 male rats with spontaneous hypertension(SHT)into an L-arginine(LA)group(n=6)and an SHT model control(MC)group(n=6),took another 6 Wistar Kyoto male rats as normal controls(NC),and treated the animals in the LA group by intraperitoneal injection of LA at 400 mg/kg and those in the latter two groups with physio-logical saline,once a day,all for 7 days.Then we observed the blood pressure and penile erection of the rats,and determined the ex-pressions of the cGMP/PKG signaling pathway-related proteins and mRNAs in different groups using ELISA,Western blot and RT-qPCR.Results:Transcriptomics combined with network pharmacology showed that the cGMP/PKG signaling pathway played a key role in hypertension-induced ED.In vivo animal experiments revealed a significantly lower frequency of penile erections in the MC than in the NC group(1.33±0.52 vs 2.67±0.51,P＜0.05).The protein expressions of eNOS,PKG and sGC were markedly de-creased in the model controls compared with those the normal controls(P＜0.05),but remarkably upregulated in the LA group com-pared with those in the MC group(P＜0.05).Conclusion:Hypertension decreases the expressions of eNOS,NO,sGC,cGMP and PKG proteins and the level of testosterone by inhibiting the cGMP/PKG signaling pathway,which consequently suppresses the relaxa-tion of the penile vascular smooth muscle and reduces erectile function.

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]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To understand the antimicrobial resistance of Escherichia spp.from member units of Hu-nan Province Antimicrobial Resistance Surveillance System from 2012 to 2021.Methods According to the technical scheme of China Antimicrobial Resistance Surveillance System(CARSS),data about Escherichia spp.and the anti-microbial susceptibility testing results reported from member units of Hunan Province Antimicrobial Resistance Sur-veillance System were analyzed by WHONET 5.6 software.Results From 2012 to 2021,a total of 476 351 clini-cally isolated Escherichia spp.were collected,475 520 of which were Escherichia coli,accounting for 99.8％;92.6％were isolated from inpatients;39.3％were isolated from urine specimens.Over the past 10 years,the proportion of Escherichia spp.in total detected pathogens remained relatively stable,ranging 20％-23％,the lowest rate was 18.7％in 2012,and the highest rate was 22.9％in 2015.In the past 10 years,the resistance rates of Escherichia spp.to ampicillin,ceftriaxone,cefotaxime and ampicillin/sulbactam were＞80％,＞47％,＞45％,and＞39％,respectively;resistance rates to piperacillin/tazobactam,cefoperazone/sulbactam,and nitrofurantoin were all＜8％,to tigecycline,amikacin,imipenem,and meropenem(except in 2012)were all＜5％.Resistance of Escherichia spp.to 22 commonly clinically used antimicrobial agents fluctuated,but overall trend decreased year by year.The resistance rates of Escherichia spp.from patients in the intensive care unit(ICU),non-ICU patients,outpatients,and emergency patients to 22 clinically commonly used antimicrobial agents were compared among different depart-ments,and the differences were statistically significant(all P＜0.05).The resistance rates of Escherichia spp.iso-lated from ICU and non-ICU patients were compared,and except for tigecycline,the resistance rates to the other 21 antimicrobial agents were statistically different(all P＜0.05).The resistance rates of Escherichia spp.isolated from patients to commonly clinically used antimicrobial agents were statistically different among patients of different age groups(all P＜0.05).Conclusion Escherichia spp.isolated from patients in different years,departments,specimens,and ages have different resistance to commonly used antimicrobial agents.It is necessary to continue to strengthen the surveillance on bacterial resistance,so as to guide the rational choice of antimicrobial agents.

Purpose::Under-foot impact loadings can cause serious lower limb injuries in many activities, such as automobile collisions and underbody explosions to military vehicles. The present study aims to compare the biomechanical responses of the mainstream vehicle occupant dummies with the human body lower limb model and analyze their robustness and applicability for assessing lower limb injury risk in underfoot impact loading environments.Methods::The Hybrid III model, the test device for human occupant restraint (THOR) model, and a hybrid human body model with the human active lower limb model were adopted for under-foot impact analysis regarding different impact velocities and initial lower limb postures.Results::The results show that the 2 dummy models have larger peak tibial axial force and higher sensitivity to the impact velocities and initial postures than the human lower limb model. In particular, the Hybrid III dummy model presented extremely larger peak tibial axial forces than the human lower limb model. In the case of minimal difference in tibial axial force, Hybrid III's tibial axial force (7.5 KN) is still 312.5% that of human active lower limb's (2.4 KN). Even with closer peak tibial axial force values, the biomechanical response curve shapes of the THOR model show significant differences from the human lower limb model.Conclusion::Based on the present results, the Hybrid III dummy cannot be used to evaluate the lower limb injury risk in under-foot loading environments. In contrast, potential improvement in ankle biofidelity and related soft tissues of the THOR dummy can be implemented in the future for better applicability.

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G⁺) or Gram-negative bacteria (G^-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G⁺ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G⁺ bacteria. Additionally, depletion of SCFAs-producing G⁺ bacteria rather than G^- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G⁺ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G⁺ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

Extracellular vesicles (EVs) have recently received much attention about the application of drug carriers due to their desirable properties such as nano-size, biocompatibility, and high stability. Herein, we demonstrate orange-derived extracellular vesicles (OEV) nanodrugs (DN@OEV) by modifying cRGD-targeted doxorubicin (DOX) nanoparticles (DN) onto the surface of OEV, enabling significantly enhancing tumor accumulation and penetration, thereby efficiently inhibiting the growth of ovarian cancer. The obtained DN@OEV enabled to inducement of greater transcytosis capability in ovarian cancer cells, which presented the average above 10-fold transcytosis effect compared with individual DN. It was found that DN@OEV could trigger receptor-mediated endocytosis to promote early endosome/recycling endosomes pathway for exocytosis and simultaneously reduce degradation in the early endosomes-late endosomes-lysosome pathway, thereby inducing the enhanced transcytosis. In particular, the zombie mouse model bearing orthotopic ovarian cancer further validated DN@OEV presented high accumulation and penetration in tumor tissue by the transcytosis process. Our study indicated the strategy in enhancing transcytosis has significant implications for improving the therapeutic efficacy of the drug delivery system.