ObjectiveTo clarify the neuroprotective effect of black Panacis Quinquefolii Radix（PQR） and explore its active ingredients， with the aim of establishing an activity-oriented quality evaluation method. MethodsTransgenic Tg（HuC∶EGFP） zebrafish was used to establish a neuronal injury model by aluminum chloride immersion. Different doses（10， 20 mg·L^-1） of PQR and black PQR ethanol extracts were administered. The neuroprotective effects of PQR and black PQR were compared by analyzing the fluorescent area and intensity of zebrafish neurons. Based on ultra-performance liquid chromatography（UPLC）， a fingerprint profile of black PQR was established， followed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. Differential components were screened using the criteria of variable importance in the projection（VIP） value>1 and P<0.05. The neuroprotective activity of 14 batches of black PQR was assessed， and Spearman correlation analysis was used to identify saponins related to neuroprotective activity， which were then validated. Based on the above results， active marker components were determined， and an UPLC method was established for their quantitation with clear content limits. ResultsPharmacological efficacy results showed that both PQR and black PQR at different doses could significantly improved neuronal damage in zebrafish. At a dose of 20 mg·L^-1， black PQR demonstrated superior efficacy（P<0.05）. The fingerprint similarities of 14 batches of black PQR were>0.94， with 26 common peaks identified. Through comparison with the reference standards， 8 components were confirmed， including peak 1（ginsenoside Rg₁）， peak 2（ginsenoside Re）， peak 5（ginsenoside Rb₁）， peak 9（ginsenoside Rd）， peak 16［ginsenoside 20（S）-Rg₃］， peak 17［ginsenoside 20（R）-Rg₃］， peak 18（ginsenoside Rk₁）， and peak 19（ginsenoside Rg₅）. The results of PCA and OPLS-DA indicated that there were differences in saponins among black PQR samples from different origins， and 12 differential components were screened. All 14 batches of black PQR exhibited good protective effects on zebrafish neurons， with Shaanxi-produced black PQR showing superior protective effects compared to the other three production regions. Spearman correlation analysis revealed that a total of 11 components， including ginsenosides 20（S）-Rg₃， 20（R）-Rg₃， Rk₁ and Rg₅， showed a significant positive correlation with the neuroprotective effect in zebrafish（P<0.05）. The activity validation results indicated that ginsenosides 20（S）-Rg₃， 20（R）-Rg₃， Rk₁ and Rg₅ were the primary components responsible for the neuroprotective effects of black PQR. Quantitative analysis showed that the content of ginsenoside 20（S）-Rg₃ in 14 batches of black PQR ranged from 0.17% to 0.52%， and the repair rate of neuronal damage ranged from 42.77% to 97.83%. ConclusionBased on the fingerprint and neuronal protective activity， the spectrum-effect related quality control model of black PQR was established， with ginsenoside 20（S）-Rg₃ as the quality control index， and the neuronal damage repair rate≥60% as the evaluation standard， the minimum limit of ginsenoside 20（S）-Rg₃ in black PQR should be≥0.20%.

ObjectiveTo assess the quality consistency of black Panacis Quinquefolii Radix（bPQR） decoction pieces prepared by atmospheric and pressurized steaming processes based on chromaticity-chemical composition-vasoactive inhibition. The ultimate goal was to screen the pressurized steaming process yielding quality equivalent to atmospheric steaming， and optimize the processing technology of bPQR. MethodsThe bPQR decoction pieces were prepared using both atmospheric and pressurized steaming processes， and the chromaticity values［lightness value（L^*）， red/green chromaticity value（a^*）， yellow/blue chromaticity value（b^*）， total chromaticity value（E^*ab）］ were measured. High performance liquid chromatography（HPLC） was employed to establish fingerprint profiles for the decoction pieces， and cluster analysis was conducted on chromaticity values and the common peak areas in fingerprint profiles to elucidate the quality relationships between the decoction pieces processed by different methods. The optimal atmospheric steaming of bPQR decoction pieces was determined through zebrafish angiogenesis inhibition experiments. The contents of ginsenosides Rg₁， Re， Rb₁， 20（S）-Rg₃， Rk₁ and Rg₅ in the decoction pieces were quantified， and Spearman correlation analysis was employed to investigate the relationship between saponin content， chromaticity， and angiogenesis inhibition activity during the steaming process. By integrating the consistency of chromaticity， saponin components and angiogenesis inhibition activity， pressurized steaming conditions with quality equivalent to the atmospheric pressure method were selected. ResultsCompared with the atmospheric steaming method， pressurized steaming resulted in faster color darkening and higher conversion rates of ginsenosides in bPQR decoction pieces. Moreover， the neovascularization inhibitory activity of bPQR decoction pieces continued to increase with the deepening of processing. Based on the effectiveness and safety， the optimal process for preparing bPQR decoction pieces with neovascularization inhibitory activity was determined to be atmospheric steaming for 21 h. All six ginsenosides tested exhibited strong to extremely strong correlations with both the chromaticity values of the decoction pieces and their neovascularization inhibitory activities. Among them， ginsenosides Rg₁， Re and Rb₁ exhibited positive correlations with chromaticity values and negative correlations with zebrafish angiogenesis inhibition activity. Conversely， ginsenosides 20（S）-Rg₃， Rk₁ and Rg₅ showed negative correlations with chromaticity values and positive correlations with zebrafish angiogenesis inhibition activity. By integrating chromaticity values， cluster analysis results， as well as the results of activity， it was determined that the quality of bPQR decoction pieces steamed under pressurized conditions of 110 ℃（0.045 MPa） for 5 h and 115 ℃（0.07 MPa） for 3 h was highly consistent with that obtained by atmospheric steaming for 21 h. ConclusionThe preparation of bPQR decoction pieces by pressurized steaming has the advantages of short preparation time， low energy consumption， and rapid saponin conversion rate， making it a viable alternative to atmospheric steaming for preparing bPQR decoction pieces. Meanwhile， the evaluation method based on chromaticity-chemical composition-activity can provide a more scientific and effective explanation of change rules in the quality during traditional Chinese medicine processing， and offer a new model for optimizing processing technology and enhancing quality control.

Objective:To measure and analyze upper lip morphology variation before and after the cross-arch fixed restoration of the maxillary implant-supported prostheses using cone- beam CT (CBCT) to provide an esthetic objective reference for maxillary edentulous patients.Methods:There were 32 maxillary edentulous patients selected in the Department of Dental Implantology, The Affiliated Stomatological Hospital of Nanjing Medical University from January 2010 to December 2023. The CBCT data of patients with maxillary full-arch implant-supported fixed prostheses were retrospectively collected before implantation (T0), at the time of radio-guide insertion (T1), and after final repair (T2). The length and thickness of the upper lip were measured and analyzed at each time point, and the correlation between the upper lip contour data and facial esthetic parameters was analyzed.Results:After the final prosthodontic treatment, the length of the upper lip was significantly increased from (21.72±2.84) mm to (24.98±2.93) mm ( t=-8.13, P<0.001) compared with that before implant treatment. The widths of the middle and vermilion of the upper lip (Sm-Hm/Ls-UP), were reduced from (13.24±1.41), (12.81±1.67) mm to (11.36±1.67), (10.21±1.69) mm, with significant differences ( t=7.79, P<0001; t=9.37, P<0.001). The lower face height (Sn-Gn) was increased from (54.52±4.95) mm to (58.70±4.42) mm, with significant differences ( t=-11.05, P<0.001). However, the nasolabial angle reduced significantly from 95.35°± 7.70°to 90.53°±7.28°( t=7.68, P<0.001). The width of the middle of the upper lip with a radiation guide was (10.94±1.24) mm, and it increased significantly compared with that after the final prosthesis treatment ( t=-0.76, P<0.05). The proportion of straight upper lip profiles accounted for 59% (19/32), and the proportion of concave upper lip profiles accounted for 41% (13/32) after the final prosthesis treatment. In addition, the results of correlation analysis showed that the nasolabial angle variation was weak and negatively correlated with residual bone height ( r=-0.37, P=0.490). Conclusions:After the treatment of the maxillary full-arch implant-supported fixed prosthesis, the length of the upper lip increases, and the thickness of the upper lip becomes significantly thin. The maxillary full-arch implant-supported fixed prostheses support upper lips to improve the patients′ side appearances.

OBJECTIVE To study the effect of fluoropezil on embryo-fetal developmental toxicity and toxicokinetics in rabbits,and provide reference for clinical medication.METHODS According to the sequence of pregnancy,pregnant rabbits were divided into five groups:vehicle control group(1%hydroxy-propyl methylcellulose+1.5%polyethylene glycol 400 aqueous solution),positive control group(cyclo-phosphamide 18 mg·kg-1),and fluoropezil(3.6,9.0 and 22.5 mg·kg-1)groups.The vehicle control group and the fluoropezil groups were ig administrated on the 6th to 18th day of gestation(GD6-18)while the positive control group was ig given cyclophosphamide on GD6-20.The pregnant rabbits were sacri-ficed on GD28,and the embryo-fetal development was detected.Sex hormone levels of pregnant rabbits on GD5,GD18 and GD28 were detected by ELISA method.Blood samples with toxokinetics were collected for concomitant toxic generation at the first and last administration,and drug concentrations in fetal,placenta and amniotic fluid were detected with liquid chromatography tandem mass spectrometry(LC-MS/MS).RESULTS Fluoropezil 3.6,9.0 and 22.5 mg·kg-1 had no significant effect on body mass,mass gain,food consumption,pregnancy outcomes,fetal appearance,viscera,skeletal and physical growth and development of pregnant rabbits.Only on GD18 or GD28,the levels of follicle stimulating hormone,estra-diol and progesterone in each dose group fluctuated to some extent.The combined toxokinetics results indicated that fluoropezil could cross the placental barrier of the rabbits,but did not accumulate in preg-nant rabbits or fetuses.Fetal mass,crown-rump length and uterus mass in the cyclophosphamide group were lower than those in the vehicle control group.The appearance and bone of the cyclophos-phamide group were positive.CONCLUSION The no observed adverse effect level(NOAEL)of fluoro-pezil toxicity on rabbit embryo-fetal development is 22.5 mg·kg-1,which is 125 times of the effective dose.At the dosage level of 22.5 mg·kg-1,Cmax is 1093 μg·L-1,and AUC(0-24 h)6650 μg·h·L-1 on GD18.

Objective:To investigate the safety and effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis and treatment of pediatric pancreaticobiliary maljunction (PBM).Methods:Data of 40 pediatric patients under 14 with PBM diagnosed and treated by ERCP at Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from November 2012 to September 2022 were collected. PBM types, ERCP-related diagnosis and treatment, adverse events and prognosis were retrospectively analyzed.Results:Nineteen cases were P-B type (joining of common bile duct with pancreatic duct), 17 were B-P type (joining of pancreatic duct with common bile duct), and 4 were complex type. Forty children with PBM underwent 50 ERCP-related operations, among which 48 procedures succeeded. One case failed during cannulation of ERCP, replaced by rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP) afterwards. There were no serious postoperative adverse events such as bleeding, perforation or death. Thirty-four patients (85%) were followed up successfully, among which 14 underwent further surgery and 20 continued conservative treatment.Conclusion:ERCP is the golden standard to diagnose pediatric PBM, and it is also safe and effective treatment for PBM.

Objective To establish evaluation of ozagrel sodium by weighted TOPSIS method so as to provide a reference for improving the rational use of ozagrel sodium.Methods Based on the drug instructions,guidelines,relevant literatures and Delphi method,the evaluation criteria for the clinical rationality of ozagrel sodium were formulated.Attribute hierarchical model(AHM)was used to assign weights to the indicators,the weighted TOPSIS method was employed to analyze and evaluate the rationality of 108 patients that discharged from the Third People's Hospital of Henan Province from January 2021 to April 2022.Results The reponse rates of two rounds of expert advice questionnaires were 100％,the authoritative coefficients(Cr)were 0.85,0.83(＞0.70),and the experts fully affirmed the items of the standard.Among the 108 cases evaluated,37 cases(34.26％)were judged to be reasonable,52 cases(48.15％)were judged to be basically reasonable and 19 cases(17.59％)were judged to be unreasonable.The main unreasonable problems were manifested in indications,the timing of administration,drug course and monitoring of efficacy and laboratory parameters.Conclusion The method of DUE of ozagrel sodium based on weighted TOPSIS is more comprehensively and intuitively.The application of ozagrel sodium in the hospital is relatively standardized,but there are problems in the course of medication,indications,and timing of administration.So it is necessary to promote the rational use by strengthening the cooperation between pharmacists and physicians,and improving pharmaceutical intervention.

ObjectiveTo investigate the prevalence of liver cirrhosis and the changing trend of the disease burden of liver cirrhosis in the Chinese population from 1990 to 2019， and to provide a data reference for formulating the prevention and treatment strategies for liver cirrhosis in China. MethodsThe Global Burden of Disease Study 2019 was used to collect the data on the incidence rate， mortality rate， disability-adjusted life years （DALY）， years of life lost （YLL）， and years lived with disability （YLD） of liver cirrhosis. The Joinpoint regression model was used to analyze the changing trend of disease burden； the age-period-cohort （APC） model was used to evaluate age， period， and cohort effects； R software BAPC package was used to predict future changes in disease burden. ResultsFrom 1990 to 2019 in China， there were increases in the numbers of liver cirrhosis cases and prevalent cases in the general population， as well as in the male and female populations， while there was a reduction in the number of deaths. From 1990 to 2019， the standardized incidence rate， standardized prevalence rate， and standardized mortality rate of liver cirrhosis in the Chinese population showed a downward trend， with a mean annual reduction of 0.62% （95% confidence interval ［CI］： -0.74% to -0.50%， t=9.99， P<0.001）， 0.44% （95%CI： -0.53% to -0.35%， t=13.18， P<0.001）， and 3.02% （95%CI： -3.12% to -2.93%， t=7.58， P<0.001）， respectively. From 1990 to 2019， the standardized DALY， YLL， and YLD rates of liver cirrhosis in the Chinese population also showed a downward trend， with a mean annual reduction of 3.27% （95%CI： -3.37% to -3.18%， t=6.22， P<0.001）， 3.32% （95%CI： -3.42% to -3.22%， t=9.31， P<0.001）， and 1.42% （95%CI： -1.49% to -1.34%， t=4.93， P<0.001）， respectively. From 1990 to 2019， the incidence rate of liver cirrhosis in the Chinese population first increased and then decreased with age， while the mortality rate showed an increasing trend， and the risks of disease onset and death showed a decreasing trend with time and birth cohort. The predictive model showed that the standardized incidence rate， prevalence rate， mortality rate， and DALY rate of liver cirrhosis in China will show a decreasing trend from 2020 to 2030. Alcohol was the most important risk factor for both male and female populations， followed by medication. ConclusionThe disease burden of liver cirrhosis in China shows a decreasing trend from 1990 to 2019， with sex and age differences， especially in the middle-aged male population. Effective measures should be taken for intervention.

Objective To investigate the application effects of cardiac resynchronization therapy(CRT)of[left bundle optimization(LOT)]and biventricular pacing(BiV)in the patients with chronic heart failure complicating left bundle branch block.Methods The single center,prospective and non-randomized controlled study method was used.Forty-two patients with heart failure meeting CRT in this center from April 2020 to April 2022 were consecutively included.Among them,32 cases adopted the BiV-CRT(BiV-CRT group)and 10 cases adopted LOT-CRT(LOT-CRT group).The pacing-making parameters,quality of life scale(SF-36)score,6-min walk test(6-MWT),ECG QRS width(QRSd),left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF)and New York cardiac function grade(NYHA)situation were collected before surgery,after surgery immediately and in postoperative 3,6,12 months.Their complica-tions and clinical outcomes were evaluated.Results The pacing threshold value in the LOT-CRT group was stable and lower than that in the BiV-CRT group(P＜0.05);QRSd in postoperative 12 months in the LOT-CRT group was shorter than that in the BiV-CRT group[(115.0±14.3)ms vs.(133.0±14.0)ms,P＜0.05]and 6-MWT was longer than that in the BiV-CRT group[(327.0±52.8)m vs.(274.0±52.8)m,P＜0.05],and the differences were statistically significant(P＜0.05);LVEF,LVEDD,NYHA cardiac grade and SF-36 score in postoperative 12 months were improved compared with those before implantation.The rehospitaliza-tion rate of heart failure in the LOT-CRT group was lower.Conclusion LOT-CRT could obtain a narrower QRS wave and longer 6-MWT than BiV-CRT.

Objective:Efficiency is a key factor in the sustainable operation of the medical insurance system.By measuring the current efficiency of the urban employee basic medical insurance system in 31 provinces in China from 2020 to 2021,it discovers possible problems,and provides reference suggestions for improving the efficiency of the system.Methods:Using the super efficiency SBM model based on unexpected output and the Malmquist index to measure the static and dynamic efficiency of employee medical in-surance in 31 provinces in China,and using Tobit regression analysis to analyze its influencing factors.Results:The overall compre-hensive efficiency of the national employee medical insurance operation is 0.826 in 2020 and 0.827 in 2021 respectively.The efficien-cy of employee medical insurance operation in the eastern region is significantly higher than that in the central and westem regions.Over 60％of provinces have inefficient operation of employee medical insurance.The overall total factor productivity of employee medical insurance operation is showing a downward trend,and the decline in technological progress is the main limiting factor.The level of economic development has a significant promotion effect on the efficiency of employee medical insurance operation,and the degree of population aging has a significant inhibitory effect on it.Conclusion:The efficiency of employee medical insurance opera-tion in China still needs to be improved,and there is a significant efficiency gap among different regions.Therefore,investment and attention should be increased in the central and western regions to bridge regional gaps and promote the equity development of medi-cal insurance.Therefore,the reform efforts should be continuously intensified to achieve technological progress.In addition,attention should also be paid to the driving role of economic development in the efficiency of employee medical insurance operation and the for-mulation of positive policies on population aging.

Objective To explore the effect of berberine on the proliferation and invasion of human colon cancer cells and its mechanism.Methods The paraffin-embedded tumor tissues and intestinal incisal tissues(control tissues)of 96 patients who underwent radical resection of colon cancer at the First Affiliated Hospital of Henan University from January 2021 to December 2022 were selected as the research subjects.The expression of hypoxia-inducible factor-1α(HIF-1α)in tumor tissues and control tissues was detected by using the immunohistochemical method,and the relationship between HIF-1α and clinicopathological features was analyzed.The human colon cancer cell line HCT116 was cultivated in normoxic and hypoxic conditions,respectively;after adhesion,the cells were divided into normoxic group,hypoxic group,normoxic combined with berberine group,and hypoxic combined with berberine group.The cells in the normoxic combined with berberine group and the hypoxic combined with berberine group were treated with 25,50,75,and 100 μmol·L-1 berberine,respectively;while the cells in the normoxic group and the hypoxic group were not treated with any drugs.At 24,48,72,and 96 hours of cultivation,the proliferation of cells in each group was detected by using the thiazolyl blue tetrazolium bromide method,respectively.Based on the above results,the most suitable drug concentration was determined as 75 μmol·L-1.At 24 hours of cultivation,the invasion of cells in the normoxic group,normoxic combined with 75 μmol·L-1 berberine group,hypoxic group,and hypoxic combined with 75 μmol·L-1 berberine group was detected by using the Transwell method;at 48 hours of cultivation,the relative expression levels of HIF-1α and vascular endothelial growth factor(VEGF)proteins in the cells in each group were detected by using Western blot.Results HIF-1α was mainly expressed in the nucleus of colon cancer tissues and control tissues.The positive expression rates of HIF-1α in control tissues and colon cancer tissues were 19.8％(19/96)and 67.7％(65/96),respectively;the positive expression rate of HIF-1α in colon cancer tissues was significantly higher than that in control tissues(x2=11.298,P＜0.05).The expression of HIF-1α in colon cancer tissues was correlated with tumor size,lymph node metastasis,and TNM staging(P＜0.05),but had no correlation with patient gender,age,tumor infiltration depth,and differentiation degree(P＞0.05).The cells in the normoxic group showed logarithmic growth after 24 hours of culture;and the addition of berberine at a concentration of 25 μmol·L-1 had no significant effect on cell proliferation(P＞0.05);compared with 0 μmol·L-1berberine,the addition of berberine at concentrations of 50 μmol·L-1 and 75 μmol·L-1 significantly reduced cell proliferation activity after 48 hours of culture(P＜0.05),and the addition of berberine at a concentration of 100 μmol·L-1 significantly reduced cell proliferation activity after 24 hours of culture(P＜0.05).After 48 hours of culture with berberine at a concentration of 25 μmol·L-1,the proliferation activity of cells in the hypoxic group was significantly higher than that in the 0 μmol·L-1 berberine(P＜0.05);compared with 0 μmol·L-1 berberine,the addition of berberine at concentrations of 50,75,and 100 μmol·L-1 significantly reduced cell proliferation activity after 24 hours of culture(P＜0.05),and the higher the concentration of berberine,the more pronounced the decrease in cell proliferation activity(P＜0.05).At the same concentration of berberine,compared with the normoxic group,the hypoxic group showed a more significant decrease in cell proliferation activity and a more pronounced slowing-down trend in cell proliferation(P＜0.05).There was no statistically significant difference in the number of cells crossing the membrane between the normoxic group and the normoxic combined with 75 μmol·L-1 berberine group(t=0.955,P＞0.05);the number of cells crossing the membrane in the hypoxic combined with 75 μmol·L-1 berberine group was significantly less than that in the hypoxic group(t=5.354,P＜0.05);the number of cells crossing the membrane in the hypoxic group was significantly more than that in the normoxic group(t=2.625,P＜0.05).There was no statistically significant difference in the relative expression levels of HIF-1α and VEGF proteins between the normoxic group and the normoxic combined with 75 μmol·L-1 berberine group(P＞0.05);the relative expression levels of HIF-1α and VEGF proteins in the hypoxic group were significantly higher than those in the normoxic group(P＜0.05);the relative expression levels of HIF-1α and VEGF proteins in the hypoxic combined with 75 μmol·L-1 berberine group were significantly lower than those in the hypoxic group(P＜0.05);there was no statistically significant difference in the relative expression levels of HIF-1α and VEGF proteins between the normoxic combined with 75 μmol·L-1 berberine group and the hypoxic combined with 75 μmol·L-1 berberine group(P＞0.05).Conclusion HIF-1α expression is associated with growth and invasion of colon cancer.Berberine may inhibit the proliferation and invasion of colon cancer cells HCT116 by regulating the expression of HIF-1α and its downstream factor VEGF.