OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

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 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:To assess the value of chromosomal microarray analysis (CMA) for the detection of low-level mosaicisms in amniotic fluid samples, and to retrospectively analyze the rare cases of mosaicisms.Methods:Chromosomal karyotype of the fetus was determined by G-banding analysis of cultured amniotic fluid cells. CMA was used to detect copy number variation of fetal chromosomes, and fluorescence in situ hybridization (FISH) was used to determine the proportion of fetal chromosomal mosaicisms in uncultured amniotic fluid cells. Results:Among 825 prenatal samples, 4 cases of true fetal mosaicisms were detected, which yielded an incidence of 0.48%. Two cases were sex chromosomal mosaicisms, and two were autosomal mosaicisms, which involved chromosomes 8 and 9, respectively. All cases were verified by G-banding analysis of cultured amniotic fluid cells, CMA, and/or FISH.Conclusion:CMA has a great value for detecting low-level mosaicisms in amniotic fluid samples, though the positive results need to be verified by other techniques and should be interpreted with caution. The review of rare cases can provide a basis for prenatal genetic counseling.

Objective:To evaluate the impact of roxadustat on thyroid function and to identify the associated factors in patients undergoing maintenance peritoneal dialysis (PD).Methods:This study was a single-center retrospective study. PD patients who received roxadustat or recombinant human erythropoietin (rHuEPO) treatment at Nanjing Drum Tower Hospital between January 2020 and June 2024 were included. The general and clinical information as well as laboratory indexes were collected. Serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were compared before and after treatment initiation. Hemoglobin (Hb) responses were also observed between the two groups. Logistic regression analysis was performed to explore the factors associated with thyroid function changes.Results:A total of 120 patients were enrolled, with an age of (55.17±16.42) years, including 66 males (55.0%). There were 81 patients received roxadustat (roxadustat group) and 39 patiens received rHuEPO (rHuEPO group). Compared to the rHuEPO group, the roxadustat group had a higher proportion of patients with diabetes ( χ 2= 4.172, P=0.041), a shorter PD vintage ( Z=-3.406, P=0.002), a lower serum level of total cholesterol ( Z=-2.082, P=0.037) and a lower level of fasting blood glucose ( Z=-2.589, P=0.010). Following treatment with roxadustat, the levels of FT4 ( Z=-5.349, P<0.01) and TSH ( Z=-3.720, P<0.01) decreased significantly. In contrast, no significant changes in FT4 or TSH levels were observed in the rHuEPO group (both P>0.05). For both roxadustat and rHuEPO groups, there were no significant changes in FT3 levels after treatment (both P>0.05). Multivariate analysis identified that higher baseline TSH (TSH≥2.27 μIU/ml, OR=1.581, 95% CI 1.196-2.089, P=0.001) and roxadustat exposure ( OR=3.432, 95% CI 1.410-8.355, P=0.007) as independent associated factors of subsequent TSH decline, and identified that higher baseline FT4 (FT4≥14.9 pmol/L, OR=1.390, 95% CI 1.162-1.662, P=0.001) and roxadustat exposure ( OR=5.798, 95% CI 2.225-15.113, P=0.001) as independent associated factors of subsequent FT4 decline. The degrees of hemoglobin changes after roxadustat or rHuEPO treatment did not differ significantly between roxadustat group and rHuEPO group ( t=-1.062, P=0.290). Of the 31 patients who underwent a second thyroid function test during roxadustat treatment, 24 continued with the original regimen, while 7 discontinued roxadustat. Among 24 patients who maintained roxadustat treatment, TSH ( Z=-0.400, P=0.689) and FT4 ( t=0.143, P=0.888) remained stable between the second and third tests. All 7 patients who discontinued roxadustat treatment showed TSH rebound and the changes of TSH levels were more significant than that in continuers ( Z=-2.505, P=0.012). FT4 recovery occurred in only 3 of them, with no significant difference in FT4 change between discontinuers and continuers ( Z=-0.685, P=0.493). Conclusions:Roxadustat commonly suppresses TSH and FT4, but not FT3, in PD patients. Baseline levels of TSH and FT4 are key associated factors of the inhibitory effect of roxadustat on thyroid function. This suppression does not intensify with prolonged exposure and is reversible after discontinuation, with TSH levels normalizing more quickly than FT4. Roxadustat-induced thyroid suppression does not compromise its efficacy in treating renal anemia.

Objective:To evaluate the diagnostic value of the vesical imaging-reporting and data system（VI-RADS）for determining muscle invasion in variant histology urothelial carcinoma（VUC）of the bladder.Methods:A retrospective analysis was performed on the pathological and imaging data of 518 bladder cancer patients admitted to Jiangsu Province Hospital between January 2013 and January 2023. Patients were stratified into pure urothelial carcinoma（PUC）group（ n = 457）and variant urothelial carcinoma（VUC）group（ n = 61）based on the presence of histological variants. In the PUC group，there were 390 males（85.3%）and 67 females（14.7%），with a mean age of（66.9 ± 11.2）years. Tumor characteristics included maximum diameter ≥ 30 mm in 149（32.6%），< 30 mm in 308（67.4%），multiple tumors in 147（32.2%），solitary in 310（67.8%），pedunculated morphology in 143（31.3%）and non-pedunculated in 314（68.7%）. Histological grading identified high-grade tumors in 319 patients（69.8%）and low-grade tumors in 138（30.2%）. Pathological stage distribution included 191 of T a（41.8%），127 of T 1（27.8%），76 of T 2（16.6%），47 of T 3（10.3%），and 16 of T 4（3.5%）patients. The VUC group included 61 patients，comprising 51 males（83.6%）and 10 females（16.4%），with a mean age of（65.8 ± 11.4）years. Tumor characteristics were maximum diameter ≥ 30 mm in 38（62.3%），< 30 mm in 23（37.7%），multiple tumors in 16（26.2%），solitary in 45（73.8%），pedunculated morphology in 11（18.0%）and non-pedunculated in 50（82.0%）. Histological grading identified high-grade tumors in 59 patients（96.7%）and low-grade tumors in 2（3.3%）. Pathological stage distribution included 3 of T a（4.9%），15 of T 1（24.6%），15 of T 2（24.6%），20 of T 3（32.8%），and 8 of T 4（13.1%）patients. No statistically significant differences were found between the two groups in gender，age，or tumor multiplicity（ P > 0.05）. Statistically significant differences were found in pathological grade，pathological stage，maximum tumor diameter，and pedunculated morphology（ P < 0.05）. Furthermore，an external validation cohort of 278 bladder cancer patients treated between February 2023 and February 2024 from multiple centers（Jiangsu Provincial People’s Hospital，The First Affiliated Hospital of Zhengzhou University，Union Hospital Tongji Medical College Huazhong University of Science and Technology，Jiangsu Provincial Hospital of Traditional Chinese Medicine，Suzhou Municipal Hospital，Huaian First People’s Hospital，Yixing People’s Hospital）was retrospectively analyzed to externally validate the performance of VI-RADS scoring in predicting muscle invasion of VUC. This cohort included a PUC subgroup of 241 patients，comprising 196 males（81.3%）and 45 females（18.7%），with a mean age of（68.0 ± 10.7）years. Tumor characteristics were maximum diameter ≥ 30 mm in 85（35.3%），< 30 mm in 156（64.7%），multiple tumors in 65（27.0%），solitary in 176（73.0%），pedunculated morphology in 76（31.5%）and non-pedunculated in 165（68.5%）. Histological grading identified high-grade tumors in 175 patients（72.6%）and low-grade tumors in 66（27.4%）. Pathological staging comprised 107 patients of T a（44.4%），78 of T 1（32.4%），22 of T 2（9.1%），22 of T 3（9.1%），and 12 of T 4（5.0%）. The VUC subgroup consisted of 37 patients，comprising 29 males（78.4%）and 8 females（21.6%），with a mean age of（70.5 ± 9.5）years. Tumor characteristics were maximum diameter ≥ 30 mm in 23（62.2%），< 30 mm in 14（37.8%），multiple tumors in 9（24.3%），solitary in 28（75.7%），pedunculated morphology in 7（18.9%）and non-pedunculated in 30（81.1%）. Histological grading identified high-grade tumors in 36 patients（97.3%）and low-grade tumors in 1（2.7%）. Pathological staging comprised 1 patient of T a（2.7%），9 of T 1（24.3%），7 of T 2（18.9%），19 of T 3（51.4%），and 1 of T 4（2.7%）. In this validation cohort，no significant differences were found in gender，age，tumor multiplicity，or pedunculated morphology between the PUC and VUC subgroups（ P > 0.05）. Significant differences were observed in pathological grade，pathological stage，and maximum tumor diameter（ P < 0.05）. Three radiologists independently reviewed and scored the multiparametric MRI（mp-MRI）in a blinded manner. Inter-reader agreement was assessed using the weighted kappa statistic. Differences in variables between the two groups were compared using t-tests，chi-square tests，or Fisher’s exact test. The diagnostic performance of VI-RADS for muscle invasion in VUC and PUC was comprehensively evaluated using receiver operating characteristic（ROC）curves，the area under the curve（AUC），and cut-off values determined by the Youden’s index. The DeLong test was used to assess whether the diagnostic performance of VI-RADS differed between VUC and PUC. Results:In the retrospective single-center cohort，the AUC of VI-RADS for assessing muscle invasion was 0.895（95% CI 0.864?0.922）in the PUC group，with a cut-off value of > 3，and the AUC was 0.896（95% CI 0.791-0.960）in the VUC group，with a cut-off value of > 3. The difference between the two groups was not statistically significant（ P = 0.986）. Using a VI-RADS score > 3 as the cut-off value，the accuracy，sensitivity，specificity，positive predictive value（PPV），and negative predictive value（NPV）for diagnosing muscle invasion status in the PUC group were 85.8%（392/457），70.5%（98/139），92.5%（294/318），80.3%（98/122），and 87.8%（294/335），respectively. The corresponding values for the VUC group were 82.0%（50/61），76.7%（33/43），94.4%（17/18），97.1%（33/34），and 63.0%（17/27）.In the retrospective multicenter cohort，the AUC of VI-RADS for assessing muscle invasion was 0.891（95% CI 0.845?0.927）in the PUC group，with a cut-off value of > 2，and the AUC was 0.898（95% CI 0.754?0.973）in the VUC group，with a cut-off value of > 3. The difference between the two groups was not statistically significant（ P = 0.897）. Using a VI-RADS score > 3 as the cut-off value，the accuracy，sensitivity，specificity，PPV，and NPV for diagnosing muscle invasion status in the PUC group were 85.9%（207/241），58.9%（33/56），94.1%（174/185），75.0%（33/44），and 88.3%（174/197），respectively. The corresponding values for the VUC group were 81.1%（30/37），77.8%（21/27），90.0%（9/10），95.5%（21/22），and 60.0%（9/15）.In the single-center cohort，the Kappa values for inter-reader agreement in assessing muscle invasion status using VI-RADS were 0.881（ P < 0.01）for the PUC group and 0.941（ P < 0.01）for the VUC group among the three readers. In the multicenter cohort，the Kappa values were 0.858（ P < 0.01）for the PUC group and 0.838（ P < 0.01）for the VUC group. Conclusions:VI-RADS demonstrates similarly high diagnostic performance for assessing muscle invasion in both PUC and VUC，which is applicable for diagnosing muscle invasion status in VUC，and shows good inter-reader agreement.

Osteoarthritis (OA), the most prevalent joint disease of late life, is closely linked to cellular senescence. Previously, we found that the senescence of fibroblast-like synoviocytes (FLS) played an essential role in the degradation of cartilage. In this work, single-cell sequencing data further demonstrated that cartilage acidic protein 1 (CRTAC1) is a critical secreted factor of senescent FLS, which suppresses mitophagy and induces mitochondrial dysfunction by regulating SIRT3 expression. In vivo, deletion of SIRT3 in chondrocytes accelerated cartilage degradation and aggravated the progression of OA. Oppositely, intra-articular injection of adeno-associated virus expressing SIRT3 effectively alleviated OA progression in mice. Mechanistically, we demonstrated that elevated CRTAC1 could bind with NRF2 in chondrocytes, which subsequently suppresses the transcription of SIRT3 in vitro. In addition, SIRT3 reduction could promote the acetylation of FOXO3a and result in mitochondrial dysfunction, which finally contributes to the degradation of chondrocytes. To conclude, this work revealed the critical role and underlying mechanism of senescent FLSs-derived CRTAC1 in OA progression, which provided a potential strategy for the OA therapy.

Objective:To investigate the feasibility and clinical efficacy of percutaneous vertebroplasty (PVP) with measured saturated bone cement injection in the treatment of elderly patients with stage Ⅱ Kümmell's disease.Methods:A retrospective analysis was conducted to analyze the clinical data of the 41 elderly patients with stage Ⅱ Kümmell's disease who had been treated at Department of Spinal Orthopedics, Zhengzhou Orthopedic Hospital from June 2017 to June 2023 by PVP with bone cement injection into the intravertebral vacuum cleft. According to the amount of bone cement injected, the patients were divided into a saturated volume group (bone cement injection metered ≥ 150% of the cleft volume preoperatively measured) in which there were 21 cases, 4 males and 17 females, aged (78.4±5.2) years and a conventional volume group (bone cement injection metered was 100% to 120% of the cleft volume preoperatively measured) in which there were 20 cases, 6 males and 14 females, aged (79.5±7.4) years. The operative time, vacuum cleft volume measured, actual volume of bone cement injected, and percentage of bone cement injected were compared between the 2 groups. Visual analogue scale (VAS) for pain and Oswestry disability index (ODI) were compared between preoperation, postoperative 3 days, and the final follow-up in the 2 groups, as well as between the 2 groups. Cement leakage and other complications were documented.Results:The differences in the preoperative general data were not statistically significant between the 2 groups, indicating comparability ( P>0.05). All the 41 elderly patients successfully completed their surgery. Follow-up time was (18.1±3.3) months. The operative time [(39.7±7.5) min], actual volume of bone cement injected [(5.6±0.9) mL], and percentage of bone cement injected (1.8%±0.3%) in the saturated volume group were all significantly greater than those in the conventional volume group [(35.5±4.9) min, (4.4±1.0) mL, and 1.2%±0.1%] ( P<0.05). Postoperatively, the incisions healed completely in all patients, with no such complications as cement-related adverse reactions. Cement leakage occurred in 2 patients in the conventional volume group, leading to lumbar pain or discomfort after activity, which was relieved by cement reinforcement and nail-rod internal fixation. VAS pain scores and ODIs at 3 d postoperatively and at the final follow-up were significantly improved in all patients compared with preoperation ( P<0.05). At the final follow-up, both VAS pain score and ODI in the saturated volume group improved significantly greater than those in the conventional volume group ( P<0.05). None of the patients had complications like cement displacement at the final follow-up. Conclusion:PVP with measured saturated bone cement injection into the intravertebral vacuum clefts is a safe and effective treatment for stage Ⅱ Kümmell's disease in elderly patients, offering a new minimally invasive option.

Objective To investigate the expression of arginase Ⅱ(ArgⅡ)in kidney tissue of rats with diabetic nephropathy(DN)and its significance in the development of DN.Methods A total of 10 male SD rats were randomly divided into the control group and the model group,with 5 rats in each group.An rat model of DN was developed by feeding with high-sugar and high-fat diet combined with intra-peritoneal injection of low-dose streptozotocin(45 mg/kg),and they were sacrificed after 11 weeks of continued feeding.The body weight,and biochemical indexes of blood and urine of rats were determined.The right kidney was weighed and histopathological examination was performed.The pathological changes of kidney tissues and protein expression of ArgⅡ and CD68+were observed,and the immunofluores-cence double staining was used to observe the distribution and expression of ArgⅡand a marker of renal macrophage activation CD68+;the protein expression of ArgⅡ,NF-κB,TNF-α and IL-6 in kidney tissues was determined by Western blot.Results Compared with the control group,the ratio of kidney weight to body weight,24-hour urine volume,24-hour urine protein,fasting blood glucose,urea nitrogen and insulin level in the model group were significantly increased(P<0.05).The renal histopathology showed that the mesangial cells of the renal glomerular were necrotic with vascular dilatation,and the renal tubular epithelial cells were steatosis and congestion.Compared with the control group,the protein expression of ArgⅡ,CD68+,NF-κB,TNF-α and IL-6 in the kidney tissues of the model group were significantly increased(P<0.05).Immunofluorescence double staining demonstrated the co-expression of ArgⅡ and CD68+in renal tissue,and the fluorescence intensities of both ArgⅡ and CD68+in the model group were significantly stronger than those in the control group(P<0.01).Conclusion The expression of ArgⅡ is increased in DN,which may be participated in the occurrence of inflammatory lesions in DN.