Glucose-6-phosphate dehydrogenase (G6PD), the first rate-limiting enzyme of the pentose phosphate pathway (PPP), is aberrantly activated in multiple types of human cancers, governing the progression of tumor cells as well as the efficacy of anticancer therapy. Here, we discovered that cyclin-dependent kinase 5 (CDK5) rewired glucose metabolism from glycolysis to PPP in breast cancer (BC) cells by activating G6PD to keep intracellular redox homeostasis under oxidative stress. Mechanistically, CDK5-phosphorylated G6PD at Thr-91 facilitated the assembly of inactive monomers of G6PD into active dimers. More importantly, CDK5-induced pho-G6PD was explicitly observed specifically in tumor tissues in human BC specimens. Pharmacological inhibition of CDK5 remarkably abrogated G6PD phosphorylation, attenuated tumor growth and metastasis, and synergistically sensitized BC cells to poly-ADP-ribose polymerase (PARP) inhibitor Olaparib, in xenograft mouse models. Collectively, our results establish the crucial role of CDK5-mediated phosphorylation of G6PD in BC growth and metastasis and provide a therapeutic regimen for BC 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 explore the clinical value of clinical combined MRI scoring scale in predicting placenta previa with pla-centa accreta spectrum disorders(PAS).Methods The clinical and MRI data of 96 pregnant women with placenta previa were ana-lyzed retrospectively,including 37 cases in the non-PAS group and 59 cases in the PAS group.In the PAS group,there were 14 cases in the placenta accreta(PA)group,33 cases in the placenta increta(PI)group and 12 cases in the placenta percreta(PP)group.The differences in clinical and imaging features of the variables between non-PAS,PA,PI,and PP groups were analyzed to establish a sco-ring scale,and the receiver operating characteristic(ROC)curves were used to calculate the critical values of the different groups.Results Ten clinical and 15 imaging features were included for evaluation,there were statistically significant differences in 14 indicators,including the number of caesarean sections,placental thickness,abnormal subplacental vessels,and short T2 signal bands within the placenta(P<0.05).Incorporate the above indicators into the MRI scoring scale.The ROC curves showed that the area under the curve(AUC)of the MRI scoring scale analyzed diagnostic non-PAS group versus PA group was 0.874,with a significance of 0.000 and a critical value of 5.5,the AUC of the PA group versus PI group was 0.784,with a significance of 0.002 and a critical value of 9.5,and the AUC of the PI group versus PP group was 0.986,with a significance of 0.000 and a critical value of 14.5.Conclusion Clini-cal combined MRI scoring scale can evaluate whether placenta previa is accompanied by PAS and evaluate the depth of PAS,which has important clinical value.

Objective:To analyze the characteristics of patients with pneumoconiosis complicated with chronic obstructive pulmonary disease (COPD), and to explore the comorbidity of pneumoconiosis and COPD and its influencing factors.Methods:From October to December 2022, 255 pneumoconiosis patients admitted to an occupational disease prevention and control hospital from January 2018 to December 2021 were selected as the study subjects. According to whether the pneumoconiosis patients were complicated with COPD or not, they were divided into pneumoconiosis and COPD comorbidity group and pneumoconiosis group. The general condition and dust exposure of the two groups of patients were analyzed, and the relationship between different types and different periods of pneumoconiosis and COPD comorbidity was analyzed by multivariate logistic regression.Results:A total of 255 subjects were collected, including 64 patients with comorbidity of pneumoconiosis and COPD, and the comorbidity rate was 25.1%. There were 186 males (72.9%) and 69 females (27.1%), ranging in age from 35 to 90 (63.79±11.79) years, and working age from 1 to 45 (20.31±10.57) years. The comorbidity of pneumoconiosis and COPD increased with the increase of working age (χ 2trend=8.19, P=0.004), and the comorbidity rate for COPD with working age of more than 30 years was 37.7% (23/61). The comorbidity rate of pneumoconiosis and COPD also increased with the increase of the stage of pneumoconiosis (χ 2trend=13.14, P<0.001), and the comorbidity rate of pneumoconiosis and COPD in the stage Ⅲ was as high as 44.0% (11/25). The cumulative dust exposure was negatively correlated with forced expiratory volume in one second/forced vital capacity (FEV 1/FVC), and the linear regression equation y=-0.04 x+78.4. Multivariate logistic regression analysis showed that the length of services ≥30 years ( OR=3.30, 95% CI: 1.15-9.52) and stageⅡ ( OR=3.05, 95% CI: 1.03-9.04) were the risk factors for comorbidity between pneumoconiosis and COPD ( P<0.05) . Conclusion:The comorbidity rate of pneumoconiosis and COPD is high. Working age, pneumoconiosis stage and cumulative dust exposure are the main influencing factors of pneumoconiosis and COPD comorbidity, so more attention should be paid to the comorbidity of pneumoconiosis and COPD.

Objective To explore the clinical value of clinical combined MRI scoring scale in predicting placenta previa with pla-centa accreta spectrum disorders(PAS).Methods The clinical and MRI data of 96 pregnant women with placenta previa were ana-lyzed retrospectively,including 37 cases in the non-PAS group and 59 cases in the PAS group.In the PAS group,there were 14 cases in the placenta accreta(PA)group,33 cases in the placenta increta(PI)group and 12 cases in the placenta percreta(PP)group.The differences in clinical and imaging features of the variables between non-PAS,PA,PI,and PP groups were analyzed to establish a sco-ring scale,and the receiver operating characteristic(ROC)curves were used to calculate the critical values of the different groups.Results Ten clinical and 15 imaging features were included for evaluation,there were statistically significant differences in 14 indicators,including the number of caesarean sections,placental thickness,abnormal subplacental vessels,and short T2 signal bands within the placenta(P<0.05).Incorporate the above indicators into the MRI scoring scale.The ROC curves showed that the area under the curve(AUC)of the MRI scoring scale analyzed diagnostic non-PAS group versus PA group was 0.874,with a significance of 0.000 and a critical value of 5.5,the AUC of the PA group versus PI group was 0.784,with a significance of 0.002 and a critical value of 9.5,and the AUC of the PI group versus PP group was 0.986,with a significance of 0.000 and a critical value of 14.5.Conclusion Clini-cal combined MRI scoring scale can evaluate whether placenta previa is accompanied by PAS and evaluate the depth of PAS,which has important clinical value.

Objective:To analyze the characteristics of patients with pneumoconiosis complicated with chronic obstructive pulmonary disease (COPD), and to explore the comorbidity of pneumoconiosis and COPD and its influencing factors.Methods:From October to December 2022, 255 pneumoconiosis patients admitted to an occupational disease prevention and control hospital from January 2018 to December 2021 were selected as the study subjects. According to whether the pneumoconiosis patients were complicated with COPD or not, they were divided into pneumoconiosis and COPD comorbidity group and pneumoconiosis group. The general condition and dust exposure of the two groups of patients were analyzed, and the relationship between different types and different periods of pneumoconiosis and COPD comorbidity was analyzed by multivariate logistic regression.Results:A total of 255 subjects were collected, including 64 patients with comorbidity of pneumoconiosis and COPD, and the comorbidity rate was 25.1%. There were 186 males (72.9%) and 69 females (27.1%), ranging in age from 35 to 90 (63.79±11.79) years, and working age from 1 to 45 (20.31±10.57) years. The comorbidity of pneumoconiosis and COPD increased with the increase of working age (χ 2trend=8.19, P=0.004), and the comorbidity rate for COPD with working age of more than 30 years was 37.7% (23/61). The comorbidity rate of pneumoconiosis and COPD also increased with the increase of the stage of pneumoconiosis (χ 2trend=13.14, P<0.001), and the comorbidity rate of pneumoconiosis and COPD in the stage Ⅲ was as high as 44.0% (11/25). The cumulative dust exposure was negatively correlated with forced expiratory volume in one second/forced vital capacity (FEV 1/FVC), and the linear regression equation y=-0.04 x+78.4. Multivariate logistic regression analysis showed that the length of services ≥30 years ( OR=3.30, 95% CI: 1.15-9.52) and stageⅡ ( OR=3.05, 95% CI: 1.03-9.04) were the risk factors for comorbidity between pneumoconiosis and COPD ( P<0.05) . Conclusion:The comorbidity rate of pneumoconiosis and COPD is high. Working age, pneumoconiosis stage and cumulative dust exposure are the main influencing factors of pneumoconiosis and COPD comorbidity, so more attention should be paid to the comorbidity of pneumoconiosis and COPD.

Objective:To explore the application effect of intelligent referral mode in examinees with major positive results in physical examinations in a health medical center.Methods:A cross-sectional study was conducted from January 2022 to December 2023 with subjects receiving physical examinations. Those subjects with major positive results from January 2022 to December 2022 in the Health Medical Center of the Second Affiliated Hospital of Chongqing Medical University were selected as the routine referral group, and those with major positive results from January 2023 to December 2023 were selected as the intelligent referral group. The routine referral group received routine health education from the chief inspector in the health medical center, suggesting them to get outpatient consultation. On the basis of ordinary referral, the intelligent referral group received health education from a referral team composed of nurses and specialists based on internet technology to digitally integrate and share patients′ medical records, examination results, imaging data and other medical information. The subects in the intelligent referral group were provided with a green channel for outpatient consultation and medical treatment immediately. The visiting rate, hospitalization rate, average visiting time, and overall satisfaction of the subjects after being notified of abnormal results were compared between the two groups. According to the positive results, the subjects were divided into four subgroups: ultrasound examination group, radiology group, clinical laboratory group and blood pressure group.Results:After the notification, there were significant differences in hospital visit rate (84.8% vs 67.2%, χ 2=168.4), hospitalization rate (48.8% vs 36.5%, χ 2=17.80), average visit time (116 min vs 301 min, Z=-15.82), and overall satisfaction score (9.70±0.62 vs 8.29±1.26, t=-33.47) between intelligent referral group and general referral group (all P<0.01). The classification statistics of major abnormal results showed that the consultation rates in subjects with ultrasound, radiology, clinical laboratory and blood pressure abnormities in the intelligent referral group were all higher than those in the general referral group (87.9% vs 70.4%, 89.9% vs 70.6%, 80.6% vs 60.2%, 57.2% vs 41.3%, respectively; χ 2=41.91, 39.37, 19.37, 6.20, all P<0.05); the hospitalization rates in subjects with ultrasound, radiology and blood pressure abnormities in the intelligent referral group were all higher than those in the general referral group (66.8% vs 64%, 55.7% vs 42.2%, 18.7% vs 11.2%, respectively; χ 2=16.86, 11.91, 8.68, all P<0.05); the mean consultation times in subjects with ultrasound, radiology and clinical laboratory abnormities in the intelligent referral group were all significantly shorter than those in the general referral group (96 min vs 308 min, 110 min vs 300 min, 122 min vs 286 min, Z=-11.38, -9.27, -7.63, all P<0.01); the overall satisfaction scores in subjects with ultrasound examination, radiology, clinical laboratory and blood pressure abnormities in the intelligent referral group were all higher than those in the general referral group (9.69±0.60 vs 8.36±1.21, 9.09±0.62 vs 8.26±1.27, 9.74±0.69 vs 8.25±1.31; 9.68±0.59 vs 8.34±1.35, respectively; t=-18.47, -18.52, -14.42, -11.77, all P<0.01). Conclusions:The application of intelligent referral mode can improve the visiting rate and hospitalization rate of examinees with major positive results of physical examination, shorten their visiting time, and thus improve their satisfaction.

Objective:To investigate the positive rate and isolate Bordetella pertussis in children with suspected whooping cough and their close family members in Zhejiang Province, and further explore the susceptibility and resistant mechanism of Bordetella pertussis to antibiotics. Methods:A total of 273 nasopharynx swabs specimens from children with suspected whooping cough in Hangzhou Children′s Hospital from May 2022 to October 2022 were collected. The strains were isolated and cultured using charcoal select agar plate. Pertussis target genes were detected by RT-PCR. E-test method was used to detect the sensitivity of Bordetella pertussis strains to different antibiotics. The mechanism of resistance of Bordetella pertussis to macrolides was analyzed by whole genome sequencing. The phylogenetic analysis of isolated strains was based on core genome multilocus sequence typing(cgMLST). Results:Among 273 clinical samples of children with suspected pertussis and their close family members, 168 samples were positive by fluorescence quantitative PCR, accounting for 61.54%, and 30 pertussis strains were successfully isolated with a positive rate of 10.98%. In addition, among the 143 samples of close family members, 54.55% (78/143) samples were positive by RT-PCR and 9.79% (14/143) samples were positive by culture, suggesting that the close family member are important in family transmission of pertussis. Besides, most of the positive samples were from mothers. The results of E-test showed that 96.67%(29/30) strains showed high resistance to azithromycin with MIC value>256 mg/L, and the resistant mechanism of azithromycin was A2047G mutation in 23S rRNA. The phylogenetic analysis based on the cgMSLT showed that the isolated strains were clustered into two new different clades.Conclusions:The positive rate of Bordetella pertussis in close family members is at a high level and the mother may be the main source of infection, which is of great significance for monitoring and laboratory detection of suspected children′s family members. Bordetella pertussis shows high resistance to macrolides in Zhejiang Province, so monitoring of the antimicrobial resistance should be further strengthened to provide theoretical basis for clinical treatment and drug guidance.

Objective:To evaluate effect of diammonium glycyrrhizinate(DG)on lipopolysaccharide(LPS)-induced TLR4/NF-κB inflammatory signaling pathway in BV2 microglial cells and to explore its potential regulatory mechanisms on ameliorating neu-roinflammation.Methods:BV2 microglia injury model was induced by LPS and treated with 20 and 60 μmol/L DG.MTS was used to determine vitality of cells.NO level secreted by cells was detected by Griess.Inflammatory factors TNF-α,IL-6,and IL-1β levels in cell supernatant were measured by ELISA.TNF-α,IL-6,IL-1β,TLR4 and MyD88 mRNA levels were detected by RT-qPCR.Western blot was used to determine expressions of TLR4,MyD88,NF-κB,p-NF-κB,IκB-α and p-IκB-α proteins of cells.Results:Compared with control group,LPS-treated BV2 microglia had significantly lower viability(P<0.05),significantly higher NO secretion(P<0.05),significantly up-regulation levels of inflammatory factors TNF-α,IL-6 and IL-1β(P<0.05),and significantly higher mRNA levels of TNF-α,IL-6,IL-1β,TLR4 and MyD88(P<0.05),TLR4,MyD88,NF-κB,p-NF-κB,IκB-α,and p-IκB-α protein expressions were significantly increased(P<0.05).Compared with LPS group,BV2 microglia intervened with different concentrations of DG had significantly higher viability(P<0.05),significantly lower NO secretion(P<0.05),significantly lower TNF-α,IL-6 and IL-1β inflammatory factors levels(P<0.05),significantly lower mRNA levels of TNF-α,IL-6,IL-1β,TLR4 and MyD88(P<0.05),and TLR4,MyD88,p-NF-κB and p-IκB-α protein expressions were significantly reduced(P<0.05).Conclusion:DG can inhibit LPS-induced neuroinflammatory responses in microglia,whose underlying mechanism is suppression of TLR4/NF-κB signaling pathway.

Objective To investigate the effect of silk fibroin hydrogel loaded with developmental endothelial locus-1(Del-1)nanoparticles on the healing of chronic skin wounds in mice.Methods The back skin of BALB/c mice(6-8 weeks old)was pressed with a magnet for 12 h and then relaxed for 12 h,for 4 consecutive days to establish a chronic pressure ulcer wound.After infliction,the mice were randomly divided into 3 groups(n=8),and the skin wounds were treated with PBS,silk fibroin hydrogel or Del-1 nanoparticles/silk fibroin hydrogel.The wound healing was recorded with camera to calculate the wound healing rate.In 9 d after treatment,HE and Masson staining were used to observe the wound healing,and immunofluorescence staining for CD 14 and TNF-α was used to compare the appearance frequency of skin macrophages and the expression of inflammatory factors.After Tert-butyl peroxide(TBHP)was used to stimulate mouse macrophage RAW 264.7 cells and mouse vascular endothelial C166 cells,C166 cells were transfected with lentival vector to overexpress Del-1.Crystal violet staining was used to observe the migration of macrophages.RT-qPCR was used to detect the expression of inflammatory factor IL-6.Results The wound healing was significantly faster in the Del-1 nanoparticles/silk fibroin hydrogel group than the silk fibroin hydrogel group and the PBS group(P＜0.01).The expression levels of TNF-α and CD14 in the wound surface were lower(P＜0.01),but collagen deposition and tissue repair were better in the Del-1 nanoparticles/silk fibroin hydrogel group than the silk fibroin hydrogel group and the PBS group(P＜0.01).In vitro experiments,macrophages migrated to endothelial cells stimulated by TBHP,but the migration rate of macrophages was significantly lower in the Del-1 overexpression group(P＜0.01).RT-qPCR confirmed that Del-1 inhibited the transcription of IL-6(P＜0.01).Conclusion Del-1 nanoparticles/silk fibroin hydrogel can significantly accelerate the healing of skin wounds,and its mechanism may be through promoting the regression of inflammation and tissue repair.