Bacterial infection is a major threat to global public health, and can cause serious diseases such as bacterial skin infection and foodborne diseases. It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time. In this work, we developed a 4-mercaptophenylboronic acid gold nanoparticles (4-MPBA-AuNPs)-functionalized hydrogel microneedle (MPBA-H-MN) for bacteria detection in skin interstitial fluid. MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min. Surface enhanced Raman spectroscopy (SERS) detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria. Overall, the capture efficiency of this method exceeded 50%. In the concentration range of 1 × 10⁷ to 1 × 10¹⁰ colony-forming units/mL (CFU/mL), the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration. Using random forest (RF)-based machine learning, bacteria were effectively distinguished with an accuracy of 97.87%. In addition, the harmless disposal of used MNs by photothermal ablation was convenient, environmentally friendly, and inexpensive. This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

Objective:To evaluate the virulence levels of carbapenem-resistant Acinetobacter baumannii ST191, ST195, and ST208, and to analyze the differences in virulence factors among these epidemic clones. Methods:The study involved the genomic sequencing of 233 Acinetobacter baumannii strains that were isolated from the Fifth Medical Center of the Chinese People′s Liberation Army General Hospital (North Hospital) between 2011 and 2019. The genomic data was cross-referenced with the Virulence Factor Database (VFDB) to examine the presence of virulence genes in the strains. Furthermore, a Galleria mellonella infection survival model was used to evaluate the virulence levels of the strains, and the association between virulence levels and virulence genes was analyzed. Results:The study included 38 strains of the ST191 clone, 104 strains of the ST195 clone, and 91 strains of the ST208 clone. In the Galleria mellonella infection survival experiment, the average mortality rate for ST191 was 23.0%, with 3 (7.9%) highly virulent strains. For ST195, the average mortality rate was 53.0%, with 34 (32.7%) highly virulent strains. For ST208, the average mortality rate was 47.0%, with 20 (21.9%) highly virulent strains. There was a significant statistical difference in mortality rates between ST191 and ST195 ( χ 2=13.9, P<0.001) as well as between ST191 and ST208 ( χ2=15.2, P<0.001). A comparison of the strains with the VFDB revealed significant differences in the virulence genes carried by the clones. Specifically, the type Ⅵ secretion system-related genes ( clpV/tssH, hcp/tssD, tagX, tssA, tssB, tssC, tssE, tssF, tssG, tssK, ssL, tssM) and the sugar transferase gene ACICU_RS00475 were found to be universally absent in ST191 strains (0%) while being prevalent in ST195 (100.0%) and ST208 (>82.0%) strains. Statistical analysis revealed an association between the mortality rate of the clones and the presence of virulence genes( clpV/tssHP<0.001, hcp/tssDP=0.001, tagXP<0.001, tssAP<0.001, tssBP=0.001, tssCP=0.001, tssE P=0.001, tssF P=0.001, tssGP<0.001, tssKP<0.001, tssLP<0.001, tssMP=0.001, ACICU_RS00475 P=0.001). Conclusion:Among the carbapenem-resistant epidemic clones of Acinetobacter baumannii, the ST191 clone shows lower mortality rates in Galleria mellonella, possibly because of the lack of type Ⅵ secretion system and sugar transferase genes.

miR-135 is a highly conserved miRNA in mammals and includes miR-135a and miR-135b.Recent studies have shown that miR-135b is a key regulatory factor in cardio-cerebrovascular diseases.It is involved in regulating the pathological process of myocardial infarction,myocardial ischemia/reperfusion injury,cardiac hypertrophy,atrial fibrillation,diabetic cardiomyopathy,atherosclerosis,pulmonary hyperten-sion,cerebral ischemia/reperfusion injury,Parkinson's disease,and Alzheimer's disease.Obviously,miR-135b is an emerging player in cardio-cerebrovascular diseases and is expected to be an important target for the treatment of cardio-cerebrovascular diseases.However,the crucial role of miR-135b in cardio-cerebrovascular diseases and its underlying mechanism of action has not been reviewed.Therefore,in this review,we aimed to comprehensively summarize the role of miR-135b and the signaling pathway mediated by miR-135b in cardio-cerebrovascular diseases.Drugs targeting miR-135b for the treatment of diseases and related patents,highlighting the importance of this target and its utility as a therapeutic target for cardio-cerebrovascular diseases,have been discussed.

Objective:To evaluate the virulence levels of carbapenem-resistant Acinetobacter baumannii ST191, ST195, and ST208, and to analyze the differences in virulence factors among these epidemic clones. Methods:The study involved the genomic sequencing of 233 Acinetobacter baumannii strains that were isolated from the Fifth Medical Center of the Chinese People′s Liberation Army General Hospital (North Hospital) between 2011 and 2019. The genomic data was cross-referenced with the Virulence Factor Database (VFDB) to examine the presence of virulence genes in the strains. Furthermore, a Galleria mellonella infection survival model was used to evaluate the virulence levels of the strains, and the association between virulence levels and virulence genes was analyzed. Results:The study included 38 strains of the ST191 clone, 104 strains of the ST195 clone, and 91 strains of the ST208 clone. In the Galleria mellonella infection survival experiment, the average mortality rate for ST191 was 23.0%, with 3 (7.9%) highly virulent strains. For ST195, the average mortality rate was 53.0%, with 34 (32.7%) highly virulent strains. For ST208, the average mortality rate was 47.0%, with 20 (21.9%) highly virulent strains. There was a significant statistical difference in mortality rates between ST191 and ST195 ( χ 2=13.9, P<0.001) as well as between ST191 and ST208 ( χ2=15.2, P<0.001). A comparison of the strains with the VFDB revealed significant differences in the virulence genes carried by the clones. Specifically, the type Ⅵ secretion system-related genes ( clpV/tssH, hcp/tssD, tagX, tssA, tssB, tssC, tssE, tssF, tssG, tssK, ssL, tssM) and the sugar transferase gene ACICU_RS00475 were found to be universally absent in ST191 strains (0%) while being prevalent in ST195 (100.0%) and ST208 (>82.0%) strains. Statistical analysis revealed an association between the mortality rate of the clones and the presence of virulence genes( clpV/tssHP<0.001, hcp/tssDP=0.001, tagXP<0.001, tssAP<0.001, tssBP=0.001, tssCP=0.001, tssE P=0.001, tssF P=0.001, tssGP<0.001, tssKP<0.001, tssLP<0.001, tssMP=0.001, ACICU_RS00475 P=0.001). Conclusion:Among the carbapenem-resistant epidemic clones of Acinetobacter baumannii, the ST191 clone shows lower mortality rates in Galleria mellonella, possibly because of the lack of type Ⅵ secretion system and sugar transferase genes.

The incidence of early-onset gastric cancer (EOGC) is consistently increasing, and its etiology is notably complex. This increase may be attributed to distinctive factors that differ from those associated with late-onset gastric cancer (LOGC), including genetic predispositions, dietary factors, gastric microbiota dysbiosis, and screening of high-risk cases. These factors collectively contribute to the onset of cancer. EOGC significantly differs from LOGC in terms of clinicopathological and molecular characteristics. Moreover, multiple differences in prognosis and clinical management also exist. This study aimed to systematically review the latest research advancements in the epidemiological characteristics, etiological factors, clinicopathological and molecular features, prognosis, and treatment modalities of EOGC.

Objective To investigate the efficacy of antibacterial photodynamic therapy(aPDT)as an adjunct to subgingival scaling and root planning in the treatment of chronic periodontitis.Methods This study followed medical ethics guidelines,and informed consent was obtained from all patients.Sixteen patients were recruited for this random-ized split-mouth controlled trial.The control group underwent subgingival scaling and root planning(SRP),while the ex-perimental group received subgingival scaling and root planing plus aPDT treatment using Perowave? with a toluidine blue O solution photosensitizer.The probing pocket depth(PD),recession,plaque index(PLI),bleeding index(BI)and proportion of positive sites of bleeding on probing(BOP)(BOP%)at all sites were examined at baseline(before treat-ment)and at 1,3 and 6 months after treatment.Results Follow-up was completed for 13 patients.On the control side,356 teeth were tested at 2 136 sites.A total of 360 teeth on the test side and 2 160 sites were included in the study.Before treatment,there was no significant difference in the baseline indicators between the two groups.After treatment,both groups showed significant improvement in clinical parameters,including PD,PLI,BI,and BOP%,compared with baseline.At 3 months,the BOP%and PLI in the experimental group were significantly lower than those in the control group(P＜0.05).The improvement in BOP%and PLI in the experimental group was significantly greater than that in the control group 3 months after treatment(P＜0.05).Conclusion aPDT,as an adjuvant treatment to SRP for chronic periodontitis,can improve gingival bleeding and control periodontal inflammation in the early stage.

OBJECTIVES: The aim of this study was to compare the anterior and posterior occlusal plane characteristics of patients with different temporomandibular joint osseous statuses. METHODS: A total of 306 patients with initial cone beam CT (CBCT) and cephalograms were included. They were divided into three groups on the basis of their temporomandibular joint osseous status: bilateral normal (BN) group, indeterminate for osteoarthrosis (I) group, and osteoarthrosis (OA) group. The anterior and posterior occlusal planes (AOP and POP) of the different groups were compared. Then, the regression equation was established after adjusting for confounding factors, and a correlation analysis between the occlusion planes and other parameters was performed. RESULTS: SNA, SNB, FMA, SN-MP, Ar-Go, and S-Go were correlated with the occlusal planes. Relative to the BN and I groups, the FH-OP of the OA group increased by 1.67° on the average, FH-POP increased by 1.42° on the average, and FH-AOP increased by 2.05° on the average. CONCLUSIONS The occlusal planes were steeper in the patients with temporomandibular osteoarthrosis than in the patients without it, and the mandible rotated downward and backward. The height of the mandibular ramus, the mandibular body length, and the posterior face height were small. In clinical practice, attention should be given to the potential risk of temporomandibular joint osteoarthrosis in such patients. In addition, SNB, FMA, SN-MP, Ar-Go, S-Go, and occlusal planes had moderate correlations.
Humans ; Dental Occlusion ; Cephalometry ; Mandible ; Temporomandibular Joint Disorders/diagnostic imaging* ; Temporomandibular Joint/diagnostic imaging* ; Osteoarthritis/diagnostic imaging* ; Mandibular Condyle

Objective:To analyze the characteristics of vocal fold vibration of normal people and patients with spasmodic dysphonia (SD) using laryngeal high speed videoendoscopy combined with glottal area wave analysis.Methods:This prospective study examined twenty healthy subjects (10 males and 10 females), 12 patients with adductor spasmodic dysphonia(AdSD) (2 males,10 females)as AdSD group and 2 patients with abductor spasmodic dysphonia(AbSD) (2 males) as AbSD group. Twelve of healthy subjects (2 males,10 females) were selected as control group according to AdSD group gender match. All the subjects were recruited from the Department of Voice, Zhongshan Hospital, Xiamen University from October 2019 to December 2020. All subjects underwent laryngeal high speed videoendoscopy and 10 vibration periods were selected from each recording and were used to quantitatively analyze the change of glottal area and vocal fold vibration parameters (Speed Quotient (SQ), Open Quotient (OQ) and Close Quotient (CQ)).Results:1. There were statistically significant differences in SQ, CQ and OQ between males and females in the healthy subjects ( t=12.28, 5.59, 5.59, P<0.05). The change of the glottal area during each vibration period in healthy subjects was relatively stable(0.19-0.42). 2. The change of the glottal area during each vibration period in AdSD subjects had larger fluctuations, with the glottal area change index fluctuating in the range of 0.31 to 0.62. The SQ value of the AdSD group was significantly lower than that of control group ( t=4.246, P<0.05). There were no significant differences in OQ and CQ between AdSD group and normal group ( t=1.064, 1.332, P>0.05); The SQ value of the AbSD group tended to increase compared to normal group. Conclusions:Laryngeal high speed videoendoscopy combined with glottal area wave analysis has a certain reference value in the studying the vibration characteristics of SD patients. SQ has good specificity.

Objective: To investigate the clinical characteristics, diagnostic approach, and treatment of infantile lactose intolerance, and to evaluate the diagnostic value of fecal pH. Methods: The feces and clinical data of all infants(less than 1 year old) diagnosed with simple diarrhea but without signs of infection were collected, who were treated at 4 Grade Ⅲ-Class-A hospitals within the period of June 2012 to June 2015 in Beijing were collected.Lactose intolerance was diagnosed based on urine galactose level, lactose tolerance test, and fecal pH.The clinical characteristics, therapeutic effects and detection methods of lactose tolerance group and intolerance group were analyzed.Then the diagnostic value of fecal pH was evaluated. Results: A total of 217 infants were enrolled in the study, consisting of 113 boys and 104 girls.Their age ranged from 3 to 330 days, 174 infants (80.2%) were less than 6 months old.Among them, 156 infants were diagnosed with lactose intolerance (71.9%), their median age 90.0 days (3-330 days), while the median age of the lactose tolerant group was 51.5 days (3-300 days). The incidence of lactose intolerance in infants less than 6 months old was 70.6%, and 76.7% in those older than 6 months.Clinical characteristics showed that more infants in the lactose intolerant group were breastfed compared with the lactose tolerant group [73/156 cases(46.8%) vs.16/61 cases(26.2%), χ²=7.666, P<0.05], the occurrence of loose foamy feces was higher in the lactose intolerant group [67/156 cases(42.9%) vs.15/61 cases (24.6%), χ²=6.287, P<0.05], the median duration of diarrhea in the lactose intolerant group was 30 days (1-210 days), and that in the lactose tolerant group was 30 days (1-300 days). The incidence of diarrhea more frequent than 10 times per day in the lactose intolerant group was 9.0% (14/156 cases), while that in the lactose tolerant group was 6.6% (4/61 cases). The rate of infection in the lactose intolerant group was similar to that in the lactose tolerant group [32/165 cases((20.5%) vs.17/61 cases(27.9%)]. The median time of recovery by feeding lactose-free formula milk was 2 days (1-60 days), recovery by feeding lactase lasted a median of 4 days (2-25 days), while recovery by using pro-biotics and dioctahedral smectite lasted a median of 2 days (1-5 days). The characteristics of fecal pH showed that mean pH value of fecal and the incidence of fecal pH<5.5 had no statistical significance between the lactose intolerant and tolerant group, between infants ≤6 months and infants>6 months, between the breastfeeding group and formula-feeding group, or between those with infection and those without infection (all P>0.05). Conclusions Infants with lactose intolerance often manifest foamy feces and tend to be breastfed.Lactose-free treatment efficacy was better than that with lactase.Clinical symptoms when combined with urine galactose level and lactose tolerance test can help diagnosis.However, the decrease of fecal pH proves to be unhelpful in aiding diagnosis.

Objective: To establish a triple-color pseudovirion-based neutralization assay (PBNA) and evaluate its capability of detecting immunogenicity of the sera generated by the immunization of HPV 9-valent vaccine. Methods: HPV pseudovirus (PsVs) 6/11/16/18/31/33/45/52/58 with the encapsidated fluorescence expressing red fluorescent plasmid N31-MCHREEY, green fluorescent N31-EGFP or blue fluorescent N31-mTagBFP were generated. The concentration of HPV PsVs and the infection titers of HPV PsVs were detected by double-antibody sandwich ELISA and TCID₅₀, respectively. The single- and triple color HPV 16/33/45 PsVs were used to detect the neutralization titers of mice sera immunized with HPV 9-valent vaccine and confirmed the accuracy and specificity of the triple-color PBNAs. Then, the single- and triple color HPV 6/11/18/31/33/45/52/58 PsVs were employed to detect the neutralization titers of cynomolgus macaques sera immunized with HPV 9-valent vaccine and determined whether the triple-color PBNAs could be applied to evaluate the immunogenicity of the sera generated by the immunization of HPV9-valent vaccine. Results: The concentration of HPV16 PsVs encapsulating green, red or blue fluorescent plasmid was 5.0 to 6.0 μg/ml and HPV6/11/18/31/33/45/52/59 triple-color HPV PsVs was about 1.0 to 3.0 μg/ml. 9 types HPV PsVs containing EGFP, Mcherry or mTagBFP reporter plasmid were obtained and the concentration can meet the need of neutralization detection. 9 types single-color fluorescent HPV PsVs had similar infectivity against 293FT cells with the infection titer values between 1×10⁴ and 1×10⁵. The results of PBNAs showed that there was no significant difference in the anti-HPV neutralization titers of mice sera induced by HPV 9-valent vaccine between single-color and triple-color HPV16/33/45 PsVs (P>0.05). Similarly, there was also no significant difference in the anti-HPV neutralization titers of cynomolgus macaques sera induced by HPV 9-valent vaccine between single-color and triple-color HPV6/11/18/31/33/45/52/58 PsVs (P>0.05). Conclusion We successfully established the triple-color PBNAs and verified the accuracy and specificity of triple-color PBNAs consistent with single-color PBNAs. The triple-color PBNAs can be applied to evaluate the immunogenicity of HPV 9-valent vaccine's immune serum.