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.

The abnormal accumulation of neutrophil extracellular traps （NETs） can promote the initiation and progression of pancreatic cancer， which is considered a potential therapeutic target for this disease. The Miraculous Pivot·Inquiry About Statement （《灵枢·口问》） have recorded the concept of "defensive qi stagnation". Based on the recognition that the function of defensive qi is similar to the immune function of neutrophils， and combining traditional Chinese medicine theory with clinical practice， it is proposed that the abnormal accumulation of NETs may be a pathological product of "defensive qi stagnation"， with the spleen being the critical site of pathology. Further exploring the application strategy of cleaning spleen and restoring defensive qi method in pancreatic cancer treatment， it is proposed to employ three approaches such as dredging method to eliminate spleen stagnation and inhibit pancreatic cancer proliferation， cleaning method to remove spleen dampness and suppress the inflammatory micro-environment， and tonifying method to strengthen Weiqi and to improve the immune microenvironment， which aims to provide new insights for the clinical treatment of pancreatic cancer with traditional Chinese medicine.

Objective:To analyze the efficacy of enzyme replacement therapy and anti-drug antibody production in children with Fabry disease.Methods:The clinical data of 7 children with Fabry disease treated with enzyme replacement therapy for more than 1 year at Children′s Hospital of Zhejiang University School of Medicine from July 2021 to June 2024 were retrospectively analyzed. The basic information and the changes of related clinical indicators before and after treatment were collected. Paired sample t test was used to compare renal function, left heart mass index, pain score and other related indexes before and after treatment. The anti-drug antibodies were detected by enzyme-linked immunosorbent assay. Results:A total of 6 boys and 1 girl were included. The age of diagnosis was (12.2±1.8) years. After 1 year of enzyme replacement therapy, the abnormal substrate globotriaosylsphingosine and brief pain inventory scores of all children were significantly lower than those before treatment ((16±11) vs. (63±42) μg/L, 22±19 vs. 45±29, t=3.88, 3.43, both P<0.05). There were no significant differences in glomerular filtration rate, urinary microalbumin to creatinine and left heart mass index before and after treatment ((124±35) vs. (136±26) ml/(min·1.73 m 2), (9.3±8.3) vs. (3.8±2.5) mg/g, (38±9) vs. (33±6) g/m 2.7, t=1.33, 1.74, 1.19, all P>0.05). Patients 4, 5 and 6 developed anti-drug antibodies at 1 month, 4 months and 1 month after medication, respectively. Patient 4 had persistently high anti-drug antibody titers (absorbance 3.65-3.73) accompanied by urticaria, elevated globotriaosylsphingosine and worsening clinical symptoms. Conclusions:The enzyme replacement therapy can effectively improve the clinical symptoms and reduce the level of globotriaosylsphingosine in children with Fabry disease. The anti-drug antibody is common in patients after long-term enzyme replacement therapy and may diminish the efficacy, which needs dynamic monitoring.

The aim of this study was to investigate the trend in testicular volume changes after orchiopexy in children with cryptorchidism. The clinical data of 854 children with cryptorchidism who underwent orchiopexy between January 2013 and December 2016 in Shenzhen Children's Hospital (Shenzhen, China) were retrospectively analyzed. The mean (standard deviation) age of the patients was 2.8 (2.5) years, and the duration of follow-up ranged from 1 year to 5 years. Ultrasonography was conducted preoperatively and postoperatively. The variables analyzed included age at the time of surgery, type of surgical procedure, laterality, preoperative testicular position, preoperative and postoperative testicular volumes, and the testicular volume ratio of them. The average testicular volumes preoperatively and at 1 year, 2 years, 3 years, and 5 years postoperatively were 0.27 ml, 0.38 ml, 0.53 ml, 0.87 ml, and 1.00 ml, respectively ( P < 0.001). The corresponding testicular volume ratios were 0.67, 0.76, 0.80, 0.83, and 0.84 ( P < 0.001). The mean volume of the undescended testes was significantly smaller than the mean normative value ( P < 0.001, lower than the 10 th percentile). The postoperative testicular volumes in children with cryptorchidism were generally lower than those in healthy boys but were still greater than the 10 th percentile and exhibited an increasing trend. The older the child is at the time of surgery, the larger the gap in volume between the affected and normal testes. Although testicular volume tends to gradually increase after orchiopexy for cryptorchidism, it could not normalizes. Earlier surgery results in affected testicular volumes closer to those of healthy boys.
Humans ; Male ; Cryptorchidism/diagnostic imaging* ; Orchiopexy ; Child, Preschool ; Testis/surgery* ; Retrospective Studies ; Organ Size ; Ultrasonography ; Infant ; Child ; Postoperative Period ; Follow-Up Studies

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 compare the preliminary efficacy and adverse events of chemoradiotherapy (CRT) with or without immunotherapy in bladder preservation therapy for localized muscle-invasive bladder cancer (MIBC) confined to the pelvis.Methods:Clinical data of 60 patients with MIBC who received CRT with or without immunotherapy for bladder preservation at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to June 2024 were retrospectively analyzed. Patients were divided into CRT plus immunotherapy group and CRT-alone group. Survival outcomes, bladder function preservation, recurrence and metastasis, as well as early and late radiation toxicities were evaluated. The Mann-Whitney U test was used for between-group comparisons. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated by the Kaplan-Meier method, and survival rates were compared by the log-rank test. Results:In the CRT plus immunotherapy group ( n=23), the median follow-up was 20 months. The median OS and median PFS were not reached. The 2-year OS, PFS, LRFS, and DMFS rates were 95.7%, 70.7%, 70.7%, and 92.9%, respectively, and 22 patients (96%) preserved normal bladder function. Patients with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 had significantly higher 1-year PFS rate than those with CPS <1 (100% vs. 66.7%, P=0.004). In the CRT-alone group ( n=37), the median follow-up was 37 months, with median OS and PFS of 68 and 19 months, respectively. The 2-year OS, PFS, LRFS, and DMFS rates were 92.0%, 41.1%, 60.9% and 81.5%, respectively, and 33 patients (89%) preserved normal bladder function. Compared with the CRT-alone group, the CRT plus immunotherapy group showed a significant improvement in PFS ( χ2=4.38, P=0.036), while no significant differences were observed in OS, LRFS, or DMFS (all P>0.05). The incidence of acute hematologic toxicity in the CRT plus immunotherapy group and CRT-alone group were 52% (12/23), 27% (10/37) respectively, and late genitourinary toxicity was 22% (5/23), 8% (3/37), respectively, with no significant differences in overall acute or late toxicities (all P>0.05). Conclusions:For localized MIBC, bladder preservation with CRT combined with immunotherapy significantly improves PFS compared with CRT alone, while maintaining comparable safety. The PD-L1 status may serve as a favorable predictor for immunotherapy efficacy.

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.

High altitude heart disease(HAHD)is a chronic mountain sickness in which the body is exposed to high altitude(＞2 500 m)hypobaric hypoxia environment for a long time.HAHD has high morbidity and poor prognosis,and pulmonary hypertension is the main causative mechanism for its develop-ment.The phosphodiesterase-5 inhibitor sildenafil has become a hot drug for the treatment of pulmonary hypertension.This paper reviews the progress of HAHD and discusses the mechanism of action and effectiveness of sildenafil in the treatment of HAHD,with a view to providing a basis for the treatment of HAHD with sildenafil.

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.