Piezo1 is a Ca²⁺-permeable mechanosensitive ion channel that plays a central role in mechanosensing and signal transduction in dental and periodontal tissues. In tooth tissue, Piezo1 is a key factor mediating dentin sensitive pain. The flow of dentinal tubule fluid induced by external stimulation can activate the Piezo1 channel on odontoblasts, triggering neuronal signals through the pannexin-1-purinergic 2X3 receptor (PANX-1-P2X3) receptor axis, resulting in pain perception. In addition, Piezo1 has a dual regulatory role in the process of pulp inflammation and repair : on the one hand, its expression is up-regulated in an inflammatory environment, which may aggravate pain sensitivity ; on the other hand, it activates the migration, proliferation and odontogenic differentiation of dental pulp stem cells by mediating Ca²⁺influx, ATP release and downstream purinergic 2X7 receptor (P2X7R), MEK / ERK signaling pathways, thereby promoting reparative dentin formation. In periodontal tissue, Piezo1 plays a central role in maintaining periodontal tissue homeostasis and regulating alveolar bone remodeling by sensing mechanical stimuli such as bite force. During orthodontic tooth movement, Piezo1 promotes osteogenic differentiation by activating Wnt / Ca²⁺, Notch and other pathways on the tension side. It affects osteoclast activity by regulating receptor activator of nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) balance on the pressure side. At the same time, Piezo1 is also a key regulator of periodontal immune microenvironment. It is expressed in immune cells such as macrophages, neutrophils and dendritic cells. Its activation can promote the polarization of macrophages to pro-inflammatory M1 type, enhance the release of pro-inflammatory factors and matrix metalloproteinases, and thus aggravate the inflammatory destruction of periodontal tissue.In view of its multiple functions, Piezo1 has become a potential therapeutic target, including local or systemic application of its inhibitors, mechanical intervention, physical therapy, gene therapy and stem cell therapy, showing a broad clinical transformation prospect in the treatment of oral diseases. In this paper, the structural characteristics, signal transduction mechanism of Piezo1 and its expression distribution, function and regulatory network in tooth tissue and periodontal tissue are reviewed, so as to provide ideas for the development of oral disease treatment strategies targeting Piezo1.

Objective To investigate the correlation between self-injurious and suicidal behavior in adolescents with depressive disorder and their non-enzymatic antioxidants and thyroid hormones.Methods A total of 93 adolescent patients with depressive disorder who were hospitalized at the Qingdao Mental Health Center from August 2023 to May 2024 were selected as the research subjects.The patients were divided into three groups:depression group(n=33),self-injurious behavior group(n=30)and a suicidal behavior.Plasma levels of non-enzymatic antioxidants and thyroid hormones were measured at admission and after 8 weeks of treatment,and their clinical symptoms were assessed by the Hamilton depression scale(HAMD)and the Hamilton anxiety scale(HAMA).Differences in plasma non-enzymatic antioxidants and thyroid function levels and scale scores were compared among three groups.Results Compared with depression group,baseline UA levels were lower in self-injurious and suicidal behavior groups.After 8 weeks of treatment,FT3 levels were higher in self-injurious group than in the suicidal behavior group,and both HAMD and HAMA scores decreased in all patients.After correction,HAMA scores were higher in suicidal behavior group than in depression group(P=0.047).Compared to baseline levels,TSH levels increased,and HAMD and HAMA scores decreased in all groups after treatment(P＜0.001).In suicidal behavior group,TBIL and FT3 levels decreased,and UA levels increased after treatment,while in depression group,FT4 levels decreased after treatment.Conclusion Non-enzymatic antioxidants may serve as potential biological markers for adolescents with depressive disorder who exhibit self-injurious and suicidal behavior.

Objective To investigate the correlation between self-injurious and suicidal behavior in adolescents with depressive disorder and their non-enzymatic antioxidants and thyroid hormones.Methods A total of 93 adolescent patients with depressive disorder who were hospitalized at the Qingdao Mental Health Center from August 2023 to May 2024 were selected as the research subjects.The patients were divided into three groups:depression group(n=33),self-injurious behavior group(n=30)and a suicidal behavior.Plasma levels of non-enzymatic antioxidants and thyroid hormones were measured at admission and after 8 weeks of treatment,and their clinical symptoms were assessed by the Hamilton depression scale(HAMD)and the Hamilton anxiety scale(HAMA).Differences in plasma non-enzymatic antioxidants and thyroid function levels and scale scores were compared among three groups.Results Compared with depression group,baseline UA levels were lower in self-injurious and suicidal behavior groups.After 8 weeks of treatment,FT3 levels were higher in self-injurious group than in the suicidal behavior group,and both HAMD and HAMA scores decreased in all patients.After correction,HAMA scores were higher in suicidal behavior group than in depression group(P=0.047).Compared to baseline levels,TSH levels increased,and HAMD and HAMA scores decreased in all groups after treatment(P＜0.001).In suicidal behavior group,TBIL and FT3 levels decreased,and UA levels increased after treatment,while in depression group,FT4 levels decreased after treatment.Conclusion Non-enzymatic antioxidants may serve as potential biological markers for adolescents with depressive disorder who exhibit self-injurious and suicidal behavior.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective:This study analyzes the clinicopathological features and prognostic factors of early-stage gastric mixed adenoneuroendocrine carcinoma (G-MANEC), which is an exceedingly rare malignancy, in an effort to provide evidence-based insights for clinical decision-making.Methods:A retrospective observational study was conducted using the clinical data of 36 patients with early-stage G-MANEC who underwent surgical resection at Zhongshan Hospital, Fudan University, from July 2014 to May 2022. The observed indicators included clinicopathological data and follow-up information on recurrence, metastasis, and overall survival (OS).Results:Among the 36 patients there were 21 males and 15 females, aged 32-84 (65±11) years. The most common initial symptoms were abdominal pain and distension (19/36, 52.8%), followed by incidental findings during physical examinations (7/36, 19.4%). Tumors were located in the proximal stomach in 13 cases (36.1%), the middle stomach in 4 cases (11.1%), and the distal stomach in 19 cases (52.8%). Average tumor diameter was (2.48±1.18) cm. Gross morphology included elevated type in 12 cases (33.3%), flat type in 20 cases (55.6%), and depressed type in 4 cases (11.1%). Ulceration was present in 12 cases (33.3%). There were 11 cases (30.6%) at T1a stage and 25 cases (69.4%) at T1b stage. Lymph node metastasis was positive in 10 cases (27.8%), and the differentiation grades of the adenocarcinoma component were Grade I, II, and III in 3 (8.3%), 10 (27.8%), and 23 (63.9%) cases, respectively. Furthermore, the proportion of neuroendocrine carcinoma component was ≥50% in 18 cases (50.0%) and <50% in 18 cases (50.0%). Lymphovascular or perineural invasion was present in 18 cases (50.0%). Lauren classification included mixed type in 10 cases (27.8%), intestinal type in 19 cases (52.8%), and diffuse type in 7 cases (19.4%), and chromogranin A (CgA) positivity was found in 20 cases (55.6%). Additionally, the Ki-67 index positivity was found in 26 cases (72.2%). Total gastrectomy was performed in 12 cases (33.3%) and partial gastrectomy in 24 cases (66.7%), with a median follow-up duration of 77.5 months. The 3-year and 5-year OS rates were 88.89% and 79.67%, respectively. Univariate analysis revealed that age, gross morphology, ulceration, proportion of neuroendocrine carcinoma component, lymphovascular or perineural invasion, and chromogranin A (CgA) positivity showed statistical significance in their association with OS ( P<0.10). Multivariate Cox regression analysis further identified ulceration (HR=7.74, 95%CI: 1.24-48.30, P=0.028) and CgA positivity (HR=21.76, 95%CI: 1.86-53.97, P=0.014) as independent risk factors of OS. Conclusions:Patients with early-stage G-MANEC are typically asymptomatic, and those with ulceration or positive CgA immunohistochemical staining tend to have a poor prognosis.