G protein-coupled receptors (GPCRs) are significant drug targets, but their potential in cancer therapy remains underexplored. Conventional GPCR agonists or antagonists have shown limited effectiveness in cancer treatment, necessitating new GPCR-targeting strategies for more effective therapies. This study discovers that Yersinia pestis LcrV, a crucial linker protein for plague infection, acts as a biased agonist of a GPCR, the formyl peptide receptor 1 (FPR1). The LcrV protein induces unique conformational changes in FPR1, resulting in G proteins being activated in a distinctive state without subunit dissociation. This leads to a biased signaling profile characterized by cyclic adenosine monophosphate (cAMP) responses and β-arrestin2 recruitment, but not calcium mobilization. In FPR1-expressing triple-negative breast cancer (TNBC) cells, LcrV bi-directionally modulates intracellular signaling pathways, downregulating extracellular signal-regulated kinases (ERK1/2) and Akt pathways while upregulating Jun N-terminal kinase (JNK) and p38 pathways. This dual modulation results in cell cycle arrest and the inhibition of TNBC cell proliferation. In TNBC xenograft mouse models, long-term LcrV treatment inhibits tumor growth more effectively than a conventional FPR1 antagonist. Additionally, LcrV treatment reprograms tumor cells by reducing stemness-associated proteins OCT4 and c-MYC. Our findings highlight the potential of biased GPCR agonists as a novel GPCR-targeting strategy for cancer treatment.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

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 evaluate the efficacy and safety of obinutuzumab combined with glucocorticoid-based therapy in patients with relapsed immune thrombotic thrombocytopenic purpura (iTTP).Methods:This study analyzed the efficacy and adverse reactions of four patients with relapsed iTTP who were treated with a combination of obinutuzumab and glucocorticoids to assess the effectiveness and safety of the treatment.Results:All four patients had a history of multiple relapses and had previously undergone treatment with rituximab and bortezomib. Three patients exhibited additional autoantibodies. Following the combined therapy, all patients achieved clinical remission, with ADAMTS13 activity returning to normal levels and inhibitors testing negative. During a median follow-up period of 11 months (range: 3–17 months), all patients maintained sustained remission. No severe adverse events were reported during treatment or follow-up.Conclusion:The combination of obinutuzumab and glucocorticoid-based therapy is effective and safe for treating relapsed iTTP.

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 investigate the association of Chinese visceral adiposity index(CVAI)and high-sensitivity C-reactive protein(hs-CRP)with the risk of digestive malignancies in the Kailuan study population,and to provide a basis for the prevention and control of digestive malignancies in the population.Methods A prospective cohort study was conducted,and a total of 94 377 Kailuan workers who participated in the 2006 health examination,had no history of cancer,and had complete data on CVAI,CRP,and related covariates were selected as the observation cohort.According to the levels of CVAI and CRP,the subjects were divided into low CVAI+CRP≤3 mg/L group[CVAI(-)CRP(-)group],low CVAI+CRP>3 mg/L group[CVAI(-)CRP(+)group],high CVAI+CRP≤3 mg/L group[CVAI(+)CRP(-)group],and high CVAI+CRP>3 mg/L group[CVAI(+)CRP(+)group].An analysis of variance was used for comparison of normally distributed continuous data between groups,and the non-parametric Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between groups;the chi-square test was used for comparison of categorical data between groups.The Cox proportional-hazards regression model was used to assess the impact of CVAI and CRP alone or in combination on the risk of digestive malignancies.Results There were significant differences between the four groups in age,male/female ratio,total cholesterol,triglycerides,high-density lipoprotein cholesterol,systolic blood pressure,diastolic blood pressure,fasting blood glucose,high-sensitivity C-reactive protein,waist circumference,body mass index,marital status,alcohol consumption,smoking,reported income,and physical exercise(all P<0.05).During a mean follow-up time of 14.08±2.76 years,2 043 new-onset cases of digestive malignancies were identified by the end of follow-up on December 31,2021.The Cox proportional-hazards regression model showed that after adjustment for CRP and other factors,compared with the low CVAI group,the high CVAI group had a hazard ratio(HR)of 1.34(95%confidence interval[CI]:1.23-1.47)for the risk of digestive malignancies.After adjustment for CVAI and other factors,compared with the CRP≤3 mg/L group,the CRP>3 mg/L group had an HR of 1.14(95%CI:1.02-1.28)for the risk of digestive malignancies.Compared with the CVAI(-)CRP(-)group(n=40 978),the CVAI(-)CRP(+)group(n=6 210),the CVAI(+)CRP(-)group(n=36 502),and the CVAI(+)CRP(+)group(n=10 687)had an HR of 1.05(95%CI:1.01-1.09,P<0.05),1.32(95%CI:1.20-1.45,P<0.05),and 1.48(95%CI:1.28-1.70,P<0.05),respectively,for the risk of digestive malignancies.As for digestive malignancies at specific locations,the CVAI(+)CRP(+)group had an increased risk of liver cancer,gastric cancer,pancreatic cancer,colorectal cancer,and small intestinal cancer with an HR of 1.35(95%CI:1.05-1.81,P<0.05),1.48(95%CI:1.09-2.00,P<0.05),1.60(95%CI:1.07-2.41,P<0.05),1.76(1.40-2.21,P<0.05),and 3.85(95%CI:1.43-10.33,P<0.05),respectively.Conclusion A high level of CVAI,a high level of CRP,and high levels of CVAI and CRP in combination can all increase the risk of digestive malignancies,among which the high levels of CVAI and CRP in combination may lead to a higher risk.

Objective To investigate the association of Chinese visceral adiposity index(CVAI)and high-sensitivity C-reactive protein(hs-CRP)with the risk of digestive malignancies in the Kailuan study population,and to provide a basis for the prevention and control of digestive malignancies in the population.Methods A prospective cohort study was conducted,and a total of 94 377 Kailuan workers who participated in the 2006 health examination,had no history of cancer,and had complete data on CVAI,CRP,and related covariates were selected as the observation cohort.According to the levels of CVAI and CRP,the subjects were divided into low CVAI+CRP≤3 mg/L group[CVAI(-)CRP(-)group],low CVAI+CRP>3 mg/L group[CVAI(-)CRP(+)group],high CVAI+CRP≤3 mg/L group[CVAI(+)CRP(-)group],and high CVAI+CRP>3 mg/L group[CVAI(+)CRP(+)group].An analysis of variance was used for comparison of normally distributed continuous data between groups,and the non-parametric Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between groups;the chi-square test was used for comparison of categorical data between groups.The Cox proportional-hazards regression model was used to assess the impact of CVAI and CRP alone or in combination on the risk of digestive malignancies.Results There were significant differences between the four groups in age,male/female ratio,total cholesterol,triglycerides,high-density lipoprotein cholesterol,systolic blood pressure,diastolic blood pressure,fasting blood glucose,high-sensitivity C-reactive protein,waist circumference,body mass index,marital status,alcohol consumption,smoking,reported income,and physical exercise(all P<0.05).During a mean follow-up time of 14.08±2.76 years,2 043 new-onset cases of digestive malignancies were identified by the end of follow-up on December 31,2021.The Cox proportional-hazards regression model showed that after adjustment for CRP and other factors,compared with the low CVAI group,the high CVAI group had a hazard ratio(HR)of 1.34(95%confidence interval[CI]:1.23-1.47)for the risk of digestive malignancies.After adjustment for CVAI and other factors,compared with the CRP≤3 mg/L group,the CRP>3 mg/L group had an HR of 1.14(95%CI:1.02-1.28)for the risk of digestive malignancies.Compared with the CVAI(-)CRP(-)group(n=40 978),the CVAI(-)CRP(+)group(n=6 210),the CVAI(+)CRP(-)group(n=36 502),and the CVAI(+)CRP(+)group(n=10 687)had an HR of 1.05(95%CI:1.01-1.09,P<0.05),1.32(95%CI:1.20-1.45,P<0.05),and 1.48(95%CI:1.28-1.70,P<0.05),respectively,for the risk of digestive malignancies.As for digestive malignancies at specific locations,the CVAI(+)CRP(+)group had an increased risk of liver cancer,gastric cancer,pancreatic cancer,colorectal cancer,and small intestinal cancer with an HR of 1.35(95%CI:1.05-1.81,P<0.05),1.48(95%CI:1.09-2.00,P<0.05),1.60(95%CI:1.07-2.41,P<0.05),1.76(1.40-2.21,P<0.05),and 3.85(95%CI:1.43-10.33,P<0.05),respectively.Conclusion A high level of CVAI,a high level of CRP,and high levels of CVAI and CRP in combination can all increase the risk of digestive malignancies,among which the high levels of CVAI and CRP in combination may lead to a higher risk.

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 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 evaluate the efficacy and safety of obinutuzumab combined with glucocorticoid-based therapy in patients with relapsed immune thrombotic thrombocytopenic purpura (iTTP).Methods:This study analyzed the efficacy and adverse reactions of four patients with relapsed iTTP who were treated with a combination of obinutuzumab and glucocorticoids to assess the effectiveness and safety of the treatment.Results:All four patients had a history of multiple relapses and had previously undergone treatment with rituximab and bortezomib. Three patients exhibited additional autoantibodies. Following the combined therapy, all patients achieved clinical remission, with ADAMTS13 activity returning to normal levels and inhibitors testing negative. During a median follow-up period of 11 months (range: 3–17 months), all patients maintained sustained remission. No severe adverse events were reported during treatment or follow-up.Conclusion:The combination of obinutuzumab and glucocorticoid-based therapy is effective and safe for treating relapsed iTTP.