Objectives:Comparative analysis of the beagles acute-phase electrocardiographic,hemodynamic,left ventricular flow field status,and energy consumption characteristics of pacing at different sites of conduction system may help to elucidate the scientific mechanism of left bundle branch pacing(LBBP)as a option of physiological pacing therapy.Methods:Eight healthy adult beagles were used in this study.Initially,an active fixation lead was implanted in the right atrial appendage,followed by implantation of another active fixation lead at the right ventricular apex,distal His bundle,and left bundle septal branch,respectively.After connecting a dual-chamber pacemaker,electrocardiographic and acute phase hemodynamic parameters under sinus rhythm,right ventricular apex pacing(RVAP),distal His bundle pacing(DHBP),and LBBP states were collected and analyzed.Three complete cardiac cycles of standard apical three-chamber color Doppler dynamic images were acquired under vector flow mapping(VFM)mode.Offline analysis was performed on obtained parameters including isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,atrial contraction period,and left ventricular intracavitary energy consumption.These parameters were compared under pacing at different sites and the linear correlations of major parameters were analyzed.Results:The QRS duration of baseline intrinsic sinus rhythm,RVAP,DHBP and LBBP were(45.0±4.0)ms,(98.4±6.2)ms,(50.0±4.5)ms and(62.0±4.7)ms,respectively.The LBBP-QRS duration was significantly wider than intrinsic sinus rhythm and DHBP,but significantly narrower than RVAP(all P<0.01).Compared with baseline AOO mode(the pacing rate was performed at 10 beats/min above the intrinsic heart rate),the change of acute phase maximum left ventricular pressure rise rate(LVdP/dtmax)in RVAP,DHBP and LBBP was([-7.89±5.67]% ),([0.74±2.05]% )and([-0.14±3.59]% ),respectively.There was no significant difference in LVdP/dtmax changes between DHBP and LBBP(P=0.667),but both pacing modalities were significantly better than RVAP(all P<0.01).The average energy consumption of the left ventricle under RVAP was significantly higher than that of intrinsic sinus rhythm,DHBP,and LBBP in isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,and atrial contraction period(all P<0.01).However,there was no statistically significant difference in energy consumption among intrinsic sinus rhythm,DHBP,and LBBP during the above five phases(all P>0.05).DHBP and LBBP did not show a significant increase in the number of left ventricular vortices,vortex area,and circulation intensity compared to intrinsic sinus rhythm,and LBBP did not show a significant increase in vortex area and circulation intensity compared to DHBP.Conclusions:Although LBBP canines significantly prolonged the paced QRS duration,it showed no significant differences in acute phase left ventricular hemodynamics,left ventricular flow field status,and energy consumption compared to intrinsic sinus rhythm and DHBP.Performance of LBBP was superior to RVAP.This study may contribute to revealing the theoretical basis of LBBP as a feasible physiological pacing therapy.

Objectives:Comparative analysis of the beagles acute-phase electrocardiographic,hemodynamic,left ventricular flow field status,and energy consumption characteristics of pacing at different sites of conduction system may help to elucidate the scientific mechanism of left bundle branch pacing(LBBP)as a option of physiological pacing therapy.Methods:Eight healthy adult beagles were used in this study.Initially,an active fixation lead was implanted in the right atrial appendage,followed by implantation of another active fixation lead at the right ventricular apex,distal His bundle,and left bundle septal branch,respectively.After connecting a dual-chamber pacemaker,electrocardiographic and acute phase hemodynamic parameters under sinus rhythm,right ventricular apex pacing(RVAP),distal His bundle pacing(DHBP),and LBBP states were collected and analyzed.Three complete cardiac cycles of standard apical three-chamber color Doppler dynamic images were acquired under vector flow mapping(VFM)mode.Offline analysis was performed on obtained parameters including isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,atrial contraction period,and left ventricular intracavitary energy consumption.These parameters were compared under pacing at different sites and the linear correlations of major parameters were analyzed.Results:The QRS duration of baseline intrinsic sinus rhythm,RVAP,DHBP and LBBP were(45.0±4.0)ms,(98.4±6.2)ms,(50.0±4.5)ms and(62.0±4.7)ms,respectively.The LBBP-QRS duration was significantly wider than intrinsic sinus rhythm and DHBP,but significantly narrower than RVAP(all P<0.01).Compared with baseline AOO mode(the pacing rate was performed at 10 beats/min above the intrinsic heart rate),the change of acute phase maximum left ventricular pressure rise rate(LVdP/dtmax)in RVAP,DHBP and LBBP was([-7.89±5.67]% ),([0.74±2.05]% )and([-0.14±3.59]% ),respectively.There was no significant difference in LVdP/dtmax changes between DHBP and LBBP(P=0.667),but both pacing modalities were significantly better than RVAP(all P<0.01).The average energy consumption of the left ventricle under RVAP was significantly higher than that of intrinsic sinus rhythm,DHBP,and LBBP in isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,and atrial contraction period(all P<0.01).However,there was no statistically significant difference in energy consumption among intrinsic sinus rhythm,DHBP,and LBBP during the above five phases(all P>0.05).DHBP and LBBP did not show a significant increase in the number of left ventricular vortices,vortex area,and circulation intensity compared to intrinsic sinus rhythm,and LBBP did not show a significant increase in vortex area and circulation intensity compared to DHBP.Conclusions:Although LBBP canines significantly prolonged the paced QRS duration,it showed no significant differences in acute phase left ventricular hemodynamics,left ventricular flow field status,and energy consumption compared to intrinsic sinus rhythm and DHBP.Performance of LBBP was superior to RVAP.This study may contribute to revealing the theoretical basis of LBBP as a feasible physiological pacing therapy.

Objective To develop a time-resolved fluorescent immunoassay kit for the rapid,accurate and quantitative detection of S100B protein in serum and to evaluate its performance.Methods The test strip was prepared using time-resolved fluorescent microsphere-labeled anti-S100B polyclonal antibody and rabbit IgG antibody,labeling pads,sample pads,S100B nitrocellulose films and absorbent paper,and an S100B time-resolved fluorescence immunoassay kit was obtained by assembling the cartridge.The performance of the kit developed was evaluated by standard curve,accuracy,minimum detection limit,linear interval,specificity,reproducibility and stability.The reference intervals of 199 pieces of healthy human serum and plasma samples from a certain region were detected with the kit,and the clinical performance of the kit and Roche Elecsys S100 kit was tested by synchronous blind method to assess the consistency of the results of the two kits for 142 samples.Results The S100B time-resolved fluorescence immunoassay kit had the standard curve beingy=(1.133 02+1.752 24)/[1+(x/1.082 20)×(-0.603 52)]-1.752 24,R2=0.999 08 and the linear range being[0.05,30]ng/mL,which met the requirements of the relative deviation of the accuracy within±15％,the minimum detection limit not hgier than 0.05 ng/mL,the relative deviation of specificity within±15％and the coefficient of variation of intra-and inter-batch difference less than 15％.The stability test results indicated that the kit was valid for 12 months at 2-30 ℃ conditions.The reference intervals of serum and plasma samples measured by the kit were both lower than 0.3 ng/mL.Clinical trials showed that the results by the kit and Roche Elecsys S100 Assay Kit were in high agreement(Kappa=0.906 1＞0.80)and met the requirements.Conclusion The kit developed detects the concentration of S100B protein in serum quickly,accurately and quantitatively,and provides references for the diagnosis and treatment of neurological diseases,autoimmune diseases,cerebrovascular diseases and etc.[Chinese Medical Equipment Journal,2024,45(1):47-55]

Objective To investigate the oral health status and caries related influence factors in 3-year-old children in Shanghai.Methods A total of 1 709 3-year-old children in 29 kindergartens from Huangpu,Xuhui,Jiading,and Jing'an districts were selected for the survey by random cluster sampling in 2021.Oral clinical examinations and questionnaires were conducted according to the criteria of the Fourth National Oral Health Epidemiological Survey.EpiData 3.1 software was used to build the database,analyse the prevalence of caries and the mean dmft.Multivariate logistic regression model was used to evaluate the influence factors of caries.Results A total of 1 709 questionnaires were collected in this survey,of which 1469 were complete questionnaires,with a valid rate of 86.0%.The prevalence of caries was 27.8%,and the mean dmft was 1.09±2.49.The caries filling rate was 8.2%.Frequency of eating sweet food(P<0.001),eating before bedtime(P=0.016),a history of dental discomfort(P<0.001),no history of dental visits within six months(P=0.015),a history of dental visits for therapeutic purposes(P<0.001),caries status of mothers(P<0.001),and parent's education level(P=0.012)were influence factors of caries in 3-year-old children.Conclusion The prevalence of caries in 3-year-old children in Shanghai is lower than the national level,but more improvement is needed.The frequency of eating sweet food,eating before bedtime,and parent's cognition of oral health are the influence factors of children's caries.

Objective To investigate the oral health status of the first-grade primary school students in Shanghai and analyze its influencing factors.Methods In 2021,Huangpu,Xuhui,Jiading,and Jing'an districts were selected in Shanghai by random sampling method.The first-grade students of 8 primary schools in these 4 districts were enrolled by random cluster sampling.Oral clinical examinations and questionnaires were conducted according to the criteria of the Fourth National Oral Health Epidemiological Survey.EpiData 3.1 software was used to create the database.SPSS 26.0 software was applied for statistical analysis.Chi-square test was used to compare the caries prevalence between groups,and two independent samples non-parametric test was used to compare the decayed,missing and filled teeth(DMFT)between groups.Multifactorial logistic regression model was used to analyzse the influencing factors of caries.Results A total of 824 informed consent forms and questionnaires were collected,of which 764 were completed,with an effective rate of 92.7％.The total caries prevalence of the participating students was 65.6％(501/764),and the mean DMFT was 3.24±3.47.A total of 2 473 carious teeth were found in the participating students,and 671 teeth were filled,with a filling rate of 27.1％.There were 7.91±2.76 permanent teeth erupted per student,and 56.3％(430/764)of the students had all 4 first permanent molars erupted.Multivariate logistic regression showed that eating sweets＞3 times a day(P=0.030),eating regularly before bedtime(P=0.001),and parents'cognition of kids'poor oral health status(P=0.025)were the influencing factors for the detection of caries in children.Conclusion The first-grade primary school students in Shanghai have high prevalence of caries.Eating sweets＞3 times a day,eating regularly before bedtime,and parents'cognition of kids'poor oral health status(P＜0.05)are the influencing factors for the detection of caries in children.

Reduced levels of retinal dopamine, a key regulator of eye development, are associated with experimental myopia in various species, but are not seen in the myopic eyes of C57BL/6 mice, which are deficient in melatonin, a neurohormone having extensive interactions with dopamine. Here, we examined the relationship between form-deprivation myopia (FDM) and retinal dopamine levels in melatonin-proficient CBA/CaJ mice. We found that these mice exhibited a myopic refractive shift in form-deprived eyes, which was accompanied by altered retinal dopamine levels. When melatonin receptors were pharmacologically blocked, FDM could still be induced, but its magnitude was reduced, and retinal dopamine levels were no longer altered in FDM animals, indicating that melatonin-related changes in retinal dopamine levels contribute to FDM. Thus, FDM is mediated by both dopamine level-independent and melatonin-related dopamine level-dependent mechanisms in CBA/CaJ mice. The previously reported unaltered retinal dopamine levels in myopic C57BL/6 mice may be attributed to melatonin deficiency.
Animals ; Disease Models, Animal ; Dopamine ; Melatonin ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Myopia ; Retina ; Sensory Deprivation

Objective:To evaluate the role of silencing information regulator 1 (SIRT1)/nuclear factors E2-related factor2 (Nrf2) signaling pathway in berberine-induced reduction of renal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 5 groups ( n=6 each) using a random number table method: sham operation group (S group), renal I/R group (RIR group), berberine+ I/R group (B group), berberine+ I/R+ SIRT1 inhibitor EX527 group (BE group) and berberine+ I/R+ Nrf2 inhibitor ATRA group (BA group). After the right kidney was removed, the left renal artery was clamped for 45 min followed by reperfusion to establish the model of renal I/R injury.In B, BE, and BA groups, berberine 100 mg·kg -1·d -1 was given for intragastric administration at 14 days before surgery.In group BE and group BA, EX527 5 mg·kg -1·d -1 and ATRA 10 mg·kg -1·d -1 were injected intraperitoneally at 3 days before surgery, respectively.The equal volume of normal saline was given for 14 consecutive days in group S and group RIR.Blood samples were collected from orbital vein at 24 h of reperfusion for measurement of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations, for determination of the interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) contents (by enzyme-linked immunosorbent assay) and expression of SIRT1, Nrf2, apoptosis-associated speck-like protein containing CARD (ASC), caspase-1, nucleotide-binding oligomerization domain-like receptor containing pyrin domain (NLRP3) (by Western blot) and for examination of the pathological changes of renal tubules (with a light microscope). The damage to the renal tubules was scored. Results:Compared with group S, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly increased in RIR, B, BE and BA groups, the expression of SIRT1, Nrf2, ASC, caspase-1 and NLRP3 was up-regulated in RIR, BE and BA groups, and the expression of SIRT1, Nrf2, caspase-1 and NLRP3 was up-regulated in group B ( P<0.05). Compared with group RIR, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly decreased in B, BE and BA groups, the expression of SIRT1 and Nrf2 in group B, Nrf2 and ASC in BE group and SIRT1, ASC and caspase-1 in BA group was up-regulated, and the expression of ASC, caspase-1 and NLRP3 in group B, SIRT1 and NLRP3 in BE group and Nrf2 in BA group was down-regulated ( P<0.05). Compared with group B, the serum concentrations of Cr and BUN, the contents of IL-1β and TNF-α and renal tubular injury score were significantly increased in BE and BA groups, the expression of ASC, caspase-1 and NLRP3 in BE and BA groups was up-regulated, and the expression of SIRT1 in BE and Nrf2 in BA groups was down-regulated ( P<0.05). Conclusion:SIRT1/Nrf2 signaling pathway is involved in the process of berberine-induced reduction of renal I/R, which is related to inhibiting pyroptosis in mice.

Purpose: Triple-negative breast cancer (TNBC) is highly malignant and has poor prognosis and a high mortality rate. The lack of effective therapy has spurred our investigation of new targets for treating this malignant cancer. Here, we identified RON (macrophage-stimulating 1 receptor) and MET (MET proto-oncogene, receptor tyrosine kinase) as a prognostic biomarker and therapeutic targets for potential TNBC treatment. Materials and Methods: We analyzed RON and MET expression in 187 primary TNBC clinical samples with immunohistochemistry. We validated the targeted therapeutic effects of RON and MET in TNBC using three tyrosine kinase inhibitors (TKIs): BMS-777607, INCB28060, and tivantinib. The preclinical therapeutic efficacy of the TKIs was mainly estimated using a TNBC xenograft model. Results: Patients with TNBC had widespread, abnormal expression of RON and MET. There was RON overexpression, MET overexpression, and RON and MET co-overexpression in 63 (33.7%), 63 (33.7%), and 43 cases (23.0%), respectively, which had poor prognosis and short survival. In vivo, the TKI targeting RON ant MET inhibited the activation of the downstream signaling molecules, inhibited TNBC cell migration and proliferation, and increased TNBC cell apoptosis; in the xenograft model, they significantly inhibited tumor growth and shrank tumor volumes. The TKI targeting RON and Met, such as BMS-777607 and tivantinib, yielded stronger anti-tumor effects than INCB28060. Conclusion RON and MET co-overexpression can be significant pathological characteristics in TNBC for poor prognosis. TKIs targeting RON and MET have stronger drug development potential for treating TNBC.

Male infertility (MI) is a complex multifactorial disease, and idiopathic infertility accounts for 30% of cases of MI. At present, the evidence for the effectiveness of empirical drugs is limited, and in vitro fertilization is costly and may increase the risk of birth defects and childhood cancers. Therefore, affected individuals may feel obliged to pursue natural remedies. Traditional Chinese medicine (TCM) may represent a useful option for infertile men. It has been demonstrated that TCM can regulate the hypothalamic-pituitary-testicular axis and boost the function of Sertoli cells and Leydig cells. TCM can also alleviate inflammation, prevent oxidative stress, reduce the DNA fragmentation index, and modulate the proliferation and apoptosis of germ cells. Furthermore, TCM can supply trace elements and vitamins, ameliorate the microcirculation of the testis, decrease the levels of serum anti-sperm antibody, and modify epigenetic markers. However, the evidence in favor of TCM is not compelling, which has hindered the development of TCM. This review attempts to elucidate the underlying therapeutic mechanisms of TCM. We also explore the advantages of TCM, differences between TCM and Western medicine, and problems in existing studies. Subsequently, we propose solutions to these problems and present perspectives for the future development of TCM.
Apoptosis ; Congenital Abnormalities ; DNA Fragmentation ; Epigenomics ; Fertilization in Vitro ; Germ Cells ; Humans ; Infertility ; Infertility, Male ; Inflammation ; Leydig Cells ; Male ; Male ; Medicine, Chinese Traditional ; Microcirculation ; Oxidative Stress ; Sertoli Cells ; Testis ; Trace Elements ; Vitamins

OBJECTIVE: To investigate the association between homocysteine and renal function as well as possible influencing factors in inpatient population. METHODS: From January 2014 to December 2015, a total of 27,025 hospitalized people who were admitted to the First Hospital of Peking University and were tested for plasma homocysteine were enrolled. Multiple linear regression model was performed to determine the relationship between homocysteine and eGFR. RESULTS: After excluding patients with cardiovascular disease and patients taking antihypertensive drugs, 6681 inpatient participants were included for analysis. After adjusting for age, blood pressure and other related factors, we found that eGFR decreased significantly(β=-0.53, SE=0.02, P<0.001) with the increase of homocysteine. Furthermore, the gender, age and renal functional state, had significant influence the relationship between homocysteine and eGFR. In women, those younger than 60 years old and renal impairment(eGFR<90 mL/[min·1.73 m~2]) population, the correlation was more significant. CONCLUSION: The association between homocysteine and eGFR is significant in inpatient population.