BACKGROUND:Studies have found that probiotics have a certain preventive and therapeutic effect on peri-implantitis,and there are further explorations in the mechanism against peri-implantitis.OBJECTIVE:To review the mechanism and clinical application of probiotics in the treatment of peri-implantitis.METHODS:Relevant literature was searched on PubMed,Web of Science,CNKI,and WanFang Data,using the search terms of"probiotics,peri-implantitis,flora imbalance,immunoregulation,inflammatory reaction,mechanism of action"in Chinese and English.A total of 90 articles were finally included.RESULTS AND CONCLUSION:Probiotics have the following mechanisms.They can activate the anti-inflammatory mechanism by inhibiting the secretion of inflammatory factors and promoting the production of anti-inflammatory factors.They can destroy the cell wall of pathogenic bacteria by secreting microbial complexes and bacteriocins,reduce the pH value of biofilms,improve the composition of microorganisms in microecology,induce the change of bacterial community structure,and restore the balance of microbial population around implants.They have immunomodulatory effects and can enhance the resistance of the host oral mucosa to pathogenic bacteria in the surrounding area of the implant.In addition,probiotics can produce antibacterial compounds,offset the adhesion of pathogenic microorganisms,and regulate immune function.Through the above mechanisms,probiotics have certain potential in the adjuvant treatment of peri-implantitis,which can improve the clinical parameters of peri-implantitis and affect the microbiota.Probiotic therapy provides a new treatment option,but more long-term prospective studies are needed to further verify its effect.

BACKGROUND:Studies have found that probiotics have a certain preventive and therapeutic effect on peri-implantitis,and there are further explorations in the mechanism against peri-implantitis.OBJECTIVE:To review the mechanism and clinical application of probiotics in the treatment of peri-implantitis.METHODS:Relevant literature was searched on PubMed,Web of Science,CNKI,and WanFang Data,using the search terms of"probiotics,peri-implantitis,flora imbalance,immunoregulation,inflammatory reaction,mechanism of action"in Chinese and English.A total of 90 articles were finally included.RESULTS AND CONCLUSION:Probiotics have the following mechanisms.They can activate the anti-inflammatory mechanism by inhibiting the secretion of inflammatory factors and promoting the production of anti-inflammatory factors.They can destroy the cell wall of pathogenic bacteria by secreting microbial complexes and bacteriocins,reduce the pH value of biofilms,improve the composition of microorganisms in microecology,induce the change of bacterial community structure,and restore the balance of microbial population around implants.They have immunomodulatory effects and can enhance the resistance of the host oral mucosa to pathogenic bacteria in the surrounding area of the implant.In addition,probiotics can produce antibacterial compounds,offset the adhesion of pathogenic microorganisms,and regulate immune function.Through the above mechanisms,probiotics have certain potential in the adjuvant treatment of peri-implantitis,which can improve the clinical parameters of peri-implantitis and affect the microbiota.Probiotic therapy provides a new treatment option,but more long-term prospective studies are needed to further verify its effect.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

This study was aimed at determining the genetic characteristics of Yersinia pestis in Subei County through differ-ential region(DFR),clustered regularly interspaced short palindromic repeats(CRISPR),and variable number tandem repeat(VNTR)analyses,to guide the tracing of plague outbreaks.The DNA of 89 Yersinia pestis strains isolated from various ani-mal in foci of Subei County from 1973 to 2017 was extracted.Primers for genotyping by DFR,CRISPR,and MLVA were used in PCR,and agarose electrophoresis was used to determine whether the amplified products were present.Genotypes were deter-mined through comparison against the DFR database of Yersinia pestis in China.The PCR products were sequenced and com-pared against the online CRISPR database for Yersinia pestis to determine the genotype.The number of VNTR repeats in each strain was calculated through capillary electrophoresis,and the minimum spanning tree was constructed with BioNumerics 7.6 according to the numbers of VNTR repeats from 89 Yersinia pestis strains in Subei County and 11 strains from a Marmota hi-malayana focus in Qinghai Province.The Yersinia pestis strains in Subei County were divided into six main genotypes by DFR:8,7,lb,5,32,and 44.The Yersinia pestis strains were divided into three gene clusters and three genotypes by CRISPR.Ca35'was the main gene cluster in Subei County;the genotype was 26';and the distribution was primarily in Dangchengwan Town,Yuerhong Township,and Shibaocheng Township.Ca7 and CaΔ5'comprised secondary gene clusters,with genotypes 22 and 24,and were distributed in Dangchengwan Town,Yuerhong Township,and Shibaocheng Township.The Yersinia pes-tis strains in Subei County were divided primarily into three clusters:the Dangchengwan Machang cluster,Yuerhong Township cluster and Dangchengwan Town cluster.Therefore,the Yersinia pestis strains in Subei County,divided into major and minor genotypes according to DFR,CRISPR and MLVA,showed different regional distribution characteristics,highly diverse geno-types,and complex population characteristics.These aspects are particularly important in tracing the sources of plague out-breaks.

Objective To investigate the impact of different cell digestion methods on the binding of a humanized monoclonal antibody targeting CD3L1(designated as 5H)to tumor cells.Methods Trypsin solution and a collagenase/neutral protease cocktail,combined with two digestion temperatures(room temperature and 37℃),were used to dissociate,passage,and collect various adherent tumor cell lines.Flow cytometry and confocal microscopy were then employed to compare differences in 5H antibody binding under different cell digestion conditions.Results Cells dissociated and passaged with trypsin solution at room temperature exhibited only weak binding to the 5H antibody,whereas those treated with the collagenase/neutral protease cocktail at room temperature showed significantly stronger binding.There were notable differences in the binding signal and the proportion of antibody-stained positive cells between the two groups(P<0.01).Additionally,cells treated with the collagenase/neutral protease cocktail exhibited antibody binding signals that were dependent on the concentration of the 5H antibody,enabling receptor occupancy analysis.Compared to digestion at room temperature,treatment at 37℃ resulted in a slight reduction in the binding of target cells to the 5H antibody,however,this difference was not statistically significant.Conclusion Trypsin digestion significantly reduces the binding of the anti-CD3L1 antibody to tumor cells,whereas the collagenase/neutral protease cocktail effectively preserves it.With an appropriate choice of digestion enzymes,the impact of digestion temperature is relatively minor.These findings suggest that optimized cell digestion protocols should be employed when studying interactions between antibody drugs and cell surface antigens.

Objective To investigate the impact of different cell digestion methods on the binding of a humanized monoclonal antibody targeting CD3L1(designated as 5H)to tumor cells.Methods Trypsin solution and a collagenase/neutral protease cocktail,combined with two digestion temperatures(room temperature and 37℃),were used to dissociate,passage,and collect various adherent tumor cell lines.Flow cytometry and confocal microscopy were then employed to compare differences in 5H antibody binding under different cell digestion conditions.Results Cells dissociated and passaged with trypsin solution at room temperature exhibited only weak binding to the 5H antibody,whereas those treated with the collagenase/neutral protease cocktail at room temperature showed significantly stronger binding.There were notable differences in the binding signal and the proportion of antibody-stained positive cells between the two groups(P<0.01).Additionally,cells treated with the collagenase/neutral protease cocktail exhibited antibody binding signals that were dependent on the concentration of the 5H antibody,enabling receptor occupancy analysis.Compared to digestion at room temperature,treatment at 37℃ resulted in a slight reduction in the binding of target cells to the 5H antibody,however,this difference was not statistically significant.Conclusion Trypsin digestion significantly reduces the binding of the anti-CD3L1 antibody to tumor cells,whereas the collagenase/neutral protease cocktail effectively preserves it.With an appropriate choice of digestion enzymes,the impact of digestion temperature is relatively minor.These findings suggest that optimized cell digestion protocols should be employed when studying interactions between antibody drugs and cell surface antigens.

Objective Observe the tongue and pulse characteristics of PCOS patients with phlegm-damp syndrome,explore a model for identifying PCOS patients with phlegm-damp syndrome,and provide certain objective tongue and pulse diagnostic indicators with TCM characteristics for clinical treatment.Methods A total of 172 medics were recruited from the Affiliated Shuguang Hospital of Shanghai University of Traditional Chinese Medicine,the Shanghai Hospital of Traditional Chinese Medicine,and Shanghai University of Traditional Chinese Medicine.Including PCOS group(including 68 cases with phlegm-damp syndrome and 38 cases without phlegm-damp syndrome),postmenstrual period group(35 with phlegm-damp syndrome),and normal control group with phlegm-damp syndrome(31).The Smart TCM-Ⅰ type of TCM physiological information analysis system was used to collect tongue image information(including parameters of tongue color and tongue coating)and pulse image information(including amplitude and time domain parameters of pulse wave).Results Comparison of tongue parameters showed that compared to the menstrual late phase group with phlegm-damp syndrome,the PCOS group with phlegm-damp syndrome showed significantly higher levels of TC H,TC TIP G,TC TIP B,and TC TIP H,but lower TC TIP S;Compared to the control group with phlegm-damp syndrome,the PCOS group with phlegm-damp syndrome exhibited significantly lower levels of TC ROOT R,TC ROOT V,CC R,CC G,CC B,CC V,CC MID R and CC MID V;Compared to the control group with phlegm-damp syndrome,the menstrual late phase group with phlegm-damps syndrome showed significantly lower levels of TC H,TC R,TC B,TC G,TC V,TC MID H,TC TIP G,TC TIP B,CC R,CC H,CC V,and CC MID H,but higher TC TIP S.The above differences were all significant(P<0.05).Comparison of pulse wave parameters showed that compared with the normal group,the PCOS group showed increased values in H4/H1 L、T4/T L、W1/T L、H2/H1 R、H4/H1 R、W1/T R、H2/H1 L,and T1/T L,while T5/T4 L was decreased;In the menstrual late-phase group,H4/H1 L、H5/H1 L、W1/T L、W1/T R、H2/H1 L、T1/T L、T4/T L、T1/T4 L、H2/H1 R,and H4/H1 R were higher,whereas T5/T4 L were lower.The above differences were all statistically significant(P<0.05).The nomogram diagnostic model for phlegm-damp syndrome of PCOS was established by combining tongue and pulse diagnosis parameters.And the model had a certain reliability.Conclusion The certain objective parameters of tongue and pulse diagnosis can help predict to a certain extent the phlegm-damp syndrome of PCOS,postmenstrual period,and normal control group with phlegm-damp syndrome and non-phlegm-dampness syndrome of PCOS.

Objective Observe the tongue and pulse characteristics of PCOS patients with phlegm-damp syndrome,explore a model for identifying PCOS patients with phlegm-damp syndrome,and provide certain objective tongue and pulse diagnostic indicators with TCM characteristics for clinical treatment.Methods A total of 172 medics were recruited from the Affiliated Shuguang Hospital of Shanghai University of Traditional Chinese Medicine,the Shanghai Hospital of Traditional Chinese Medicine,and Shanghai University of Traditional Chinese Medicine.Including PCOS group(including 68 cases with phlegm-damp syndrome and 38 cases without phlegm-damp syndrome),postmenstrual period group(35 with phlegm-damp syndrome),and normal control group with phlegm-damp syndrome(31).The Smart TCM-Ⅰ type of TCM physiological information analysis system was used to collect tongue image information(including parameters of tongue color and tongue coating)and pulse image information(including amplitude and time domain parameters of pulse wave).Results Comparison of tongue parameters showed that compared to the menstrual late phase group with phlegm-damp syndrome,the PCOS group with phlegm-damp syndrome showed significantly higher levels of TC H,TC TIP G,TC TIP B,and TC TIP H,but lower TC TIP S;Compared to the control group with phlegm-damp syndrome,the PCOS group with phlegm-damp syndrome exhibited significantly lower levels of TC ROOT R,TC ROOT V,CC R,CC G,CC B,CC V,CC MID R and CC MID V;Compared to the control group with phlegm-damp syndrome,the menstrual late phase group with phlegm-damps syndrome showed significantly lower levels of TC H,TC R,TC B,TC G,TC V,TC MID H,TC TIP G,TC TIP B,CC R,CC H,CC V,and CC MID H,but higher TC TIP S.The above differences were all significant(P<0.05).Comparison of pulse wave parameters showed that compared with the normal group,the PCOS group showed increased values in H4/H1 L、T4/T L、W1/T L、H2/H1 R、H4/H1 R、W1/T R、H2/H1 L,and T1/T L,while T5/T4 L was decreased;In the menstrual late-phase group,H4/H1 L、H5/H1 L、W1/T L、W1/T R、H2/H1 L、T1/T L、T4/T L、T1/T4 L、H2/H1 R,and H4/H1 R were higher,whereas T5/T4 L were lower.The above differences were all statistically significant(P<0.05).The nomogram diagnostic model for phlegm-damp syndrome of PCOS was established by combining tongue and pulse diagnosis parameters.And the model had a certain reliability.Conclusion The certain objective parameters of tongue and pulse diagnosis can help predict to a certain extent the phlegm-damp syndrome of PCOS,postmenstrual period,and normal control group with phlegm-damp syndrome and non-phlegm-dampness syndrome of PCOS.

Objective:To explore the diagnostic value of cardiac color Doppler ultrasonography for left ventricular hypertrophy(LVH)complicated left heart failure(LHF).Methods:A total of 117 LVH patients complicated LHF admitted in Ningde City Hospital Affiliated to Ningde Normal College between January 2019 and January 2023(heart failure group)and 100 healthy people(control group)who underwent general physical examination in our hospital simultaneously were selected for the study.Left ventricular ejection fraction(LVEF),left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDd),early diastolic peak flow velocity/late diastolic peak flow velocity(E/A)were measured by cardiac color Doppler ultrasound in two groups.Receiver operating charac-teristic(ROC)curve was used to analyze the diagnostic value of cardiac color Doppler ultrasound indexes for LVH complicated LHF.In addition,the 117 patients with LVH and LHF were divided into mild group(n=54)and moderate to severe group(n=63)according to cardiac function class.Spearman correlation analysis was used to an-alyze the associationof cardiac color ultrasound parameters with cardiac function class.Results:Compared with par-ticipants in control group,those in heart failure group had significant lower LVEF[(47.88±4.75)％ vs.(69.81±5.64)％],and significant higher LAD[(44.03±4.88)mm vs.(27.56±2.76)mm vs.],LVEDd[(55.68±5.04)mm vs.(42.19±1.38)mm],E/A[(13.04±3.58)vs.(6.60±1.67)](P＜0.001 all).ROC analysis indicated that the area under the curve(AUC)of the combination of various parameters of cardiac ultrasound for diagnosing LVH with LHF was significantly higher than those of the single tests(Combined detection:AUC=0.901,95％CI 0.853～0.937 vs LVEF:AUC=0.644,95％CI 0.577～0.708,LAD:AUC=0.703,95％CI 0.637～0.763,LVEDd:AUC=0.633,95％CI 0.565～0.697,E/A:AUC=0.748,95％CI 0.685～0.804,Z=7.062,5.764,7.292,4.864,P＜0.001 all).Compared with patients in mild group,those in moderate to severe group had signifi-cant lower LVEF[(45.67±3.37)％ vs.(50.47±4.86)％],and significant higher LAD[(46.31±4.42)mm vs.(41.36±3.98)mm],LVEDd[(60.09±1.75)mm vs.(50.53±1.41)mm]and E/A[(13.99±2.96)vs.(11.93±3.92)](P＜0.01 all).Spearman correlation analysis indicated that LVEF was negatively correlated with cardiac function class(r=-0.474),while LAD(r=0.511),LVEDd(r=0.863),E/A(r=0.269)were positively corre-lated with cardiac function class(P＜0.01 all).Conclusion:Cardiac color Doppler ultrasound could better diagnose LVH complicated LHF,and also could effectively predict the cardiac function of patients with LVH and LHF.

Objective To evaluate the pharmacokinetics(PK)and pharmacodynamics(PD)of propofol injectable emulsion,and to assess the bioequivalence of test and reference formulations in healthy Chinese adult volunteers.Methods Thirty-two healthy Chinese adult volunteers were recruited and randomly assigned to a fasting.single-dose,two-period and double-crossover study.Propofol was given to eligible subjects at a speed of 30 μg·kg-1·min-1 for 30 min.The concentration of propofol in plasma was determined by avalidated high performance liquid chromatography-tandem mass spectrometery(HPLC-MS/MS)method.The PK parameters of the two preparations were calculated.Bispectral index(BIS)was measured to calculate the PD parameters of two formulations.Adverse events during the trial were recorded.Results Thirty-one volunteers were included in the pharmacokinetic parameter set.The mean values of PK parameters of test andreference formulations were as follows:Cmax were(660.87±110.25)and(683.13±125.75)ng·mL-1;AUC0-t were(473.50±86.03)and(478.40±80.25)h·ng·mL-1;AUC0-∞ were(500.45±96.49)and(507.84±88.00)h·ng·mL-1;tmax were 0.47(0.25,0.53)and 0.50(0.40,0.54)h;t1/2 were(2.97±1.74)and(3.08±1.82)h.Thirty-one volunteers were included in the bioequivalence set.The 90％confidence intervals(CI)for the geometric mean ratios of Cmax,AUC0-t,AUC0-∞ were 92.64％-101.39％,96.43％-101.00％,95.67％-100.70％,respectively.The mean values of PD parameters of test and reference formulations were as follows:BISmin were(75.94±13.66)and(74.39±12.32);BISAUC0-60minwere 5 569.85±182.78 and 5 575.68±166.19;T-BISmin were 23.00 and 29.00 min,respectively.There were no serious adverse events.Conclusion Two formulations of propofol injectable emulsion were bioequivalent and both of them exhibited good safety.