BACKGROUND:Prolyl hydroxylase domain 2(PHD2)inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats.cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University.It is effective in the treatment of renal anemia with few side effects,but its effect on bone formation and bone resorption is still unclear. OBJECTIVE:To investigate the effects of cpd17 on mouse osteogenic precursor cells. METHODS:Osteogenic precursor cells were treated with cpd17.Alkaline phosphatase activity and extracellular matrix mineralization were measured,and the expression levels of osteogenesis-and osteoclastogenesis-related markers,as well as PHD2 and hypoxia-inducible factor 1α,were detected.After inhibition of the hypoxia-inducible factor 1α pathway using LW6(a hypoxia-inducible factor 1α pathway inhibitor),alkaline phosphatase activity and extracellular matrix mineralization were detected again,as well as the expression levels of osteogenesis-and osteoclastogenesis-related markers,PHD2 and hypoxia-inducible factor 1α. RESULTS AND CONCLUSION:cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization,up-regulated the expression of osteogenesis-related markers,down-regulated the expression of osteoclastogenesis-related markers,up-regulated the expression of hypoxia-inducible factor 1α,down-regulate the expression of PHD2.However,cpd17's effects were significantly attenuated by LW6.To conclude,the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway.

This study aimed to investigate halofuginone's inhibitory effect and mechanism on the activity of hepatocellular carcinoma cells. HepG2 cells were used to detect the effects of halofuginone. After treatment, cell activity, cell migration, cell cycle, and cell apoptosis were detected by CCK-8, transwell, and flow cytometry, respectively. The expression levels of growth and metabolism-related factors such as citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and isocitrate deoxygenase (IDH) were detected by real-time quantitative PCR and Western blot. Compared with the control group, the activity of HepG2 cells was significantly inhibited by halofuginone (P < 0.01), the migration rate of HepG2 cells was decreased (P < 0.01), the apoptosis of HepG2 cells was induced (P < 0.01), and the cell cycle was arrested in S phase (P < 0.01). The expression levels of tricarboxylic acid key enzymes CS, IDH3, and OGDH were up-regulated, the expression level of isocitrate dehydrogenase isoenzymes IDH1 and IDH2 were down-regulation. In conclusion, halofuginone can inhibit the proliferation and migration of HepG2 cells and promote apoptosis in a dose-dependent manner, which may be due to the promotion of the aerobic metabolism of cells.

Objective To analyze the influencing factors for catheter-associated infection(CAI)in chemotherapy treated patients after indwelling peripherally inserted central catheter(PICC)based on a random forest model.Methods 400 tumor patients who received chemotherapy and PICC were selected and divided into the training set(n=300)and the test set(n=100)in a 3∶1 ratio through computer-generated random number.Patients in the training set were subdivided into the non-infection group and the infection group based on the occurrence of infec-tion.Clinical data from two groups of patients were compared.Influencing factors for the occurrence of CAI after PICC were analyzed with multivariate logistic regression model and the integrated classification algorithm of random forest model,and the predictive performance of the two methods was compared.Results Among 300 chemotherapy treated patients in the training set,32 cases(10.67％)experienced CAI.Compared with the non-infection group,patients in the infection group had more single punctures for catheterization,longer PICC retention time,larger pro-portion of catheter movement,larger proportion of complication with diabetes,higher frequency of dressing chan-ges,lower white blood cell count and immune function(all P＜0.05).PICC retention time,catheter movement,complication with diabetes,dressing change frequency,white blood cell(WBC)and immune function were inde-pendent influencing factors for CAI after PICC(all P＜0.05).The random forest model showed that ranking by the importance of different influencing factors was as following:PICC retention time,catheter movement,complication with diabetes,WBC,dressing change frequency and immune function.The integrated classification algorithm of random forest model for predicting the occurrence of CAI in chemotherapy treated patients showed that the area un-der the receiver operating characteristic(ROC)curve(AUC)was 0.872,which had better prediction performance compared with the logistic regression model(AUC=0.791).Conclusion PICC retention time,catheter movement,complicated with diabetes,dressing change frequency,WBC level and immune function are independent influencing factors for CAI in chemotherapy treated patients.The integrated classification algorithm of random forest model can be used to predict CAI in chemotherapy treated patients,and its prediction performance is better than that of the logistic regression model.

Objective To investigate the factors influencing the prognosis of complex intracranial aneurysms treated with pipeline flow-directed device(PED)and to develop a nomogram prediction model.Methods The clinical data of a total of 98 patients with complex intracranial aneurysm,who were admitted to the Anyue County People's Hospital or the Second Affiliated Hospital of Guilin Medical College of China from January 2021 to April 2023 to receive PED treatment,were retrospectively analyzed.The influencing factors that might affect the prognosis of patients with complex intracranial aneurysm were collected.According to the modified Rankin Scale(mRS)score,the patients were divided into good prognosis group(being defined as mRS ≤2 points)and poor prognosis group(being defined as mRS＞2 points).The clinical data were compared between the two groups,and a nomogram model was established and validated.Results In the 98 patients,poor prognosis was seen in 10(10.20％).The differences in age,history of hypertension,history of diabetes mellitus,clopidogrel resistance,Fisher classification,repeated aneurysm rupture,aneurysm location,aneurysm size,aneurysm neck,multiple lesions,and Hunt-Hess grade on admission between good prognosis group and poor prognosis group were statistically significant(all P＜0.05).Multivariate analysis revealed that history of hypertension,clopidogrel resistance,repeated aneurysm rupture,aneurysm location,multiple lesions,and Hunt-Hess grade were the independent factors influencing the prognosis of patients with complex intracranial aneurysm after receiving PED treatment.The AUC of the nomogram model in predicting the prognosis of PED for complex intracranial aneurysms was 0.849(95％CI=0.758-0.939).The predicted curves of the model group and validation group were basically fitted to the standard curves.The results of the decision curve analysis showed that the net benefit to patients was greater than 0 when the probability threshold of the nomogram model for predicting a poor prognosis of PED for complex intracranial aneurysms was 0.10-0.90.Conclusion The factors causing poor prognosis of PED for complex intracranial aneurysms mainly include history of hypertension,clopidogrel resistance,repeated aneurysm rupture,etc.The nomogram model established in this study can predict the risk of poor prognosis in patients with complicated intracranial aneurysm after receiving PED treatment.

Objectives:To examine the functional outcomes of robot-assisted radical prostatectomy (RARP) with preservation of pelvic floor stabilized structure and early elevated retrograde liberation of the neurovascular bundle (PEEL).Methods:This study was a retrospective cohort study. Between June 1, 2022, and March 20, 2023, 27 cases of RARP with PEEL and 153 cases of RARP with preservation of pelvic floor stabilized structure (PPSS) were included in this study. All patients were males, aged (62.5±5.2) years (range: 50 to 73 years). There were 18 cases of ≤T2b stage and 9 cases of T2c stage. After 1∶1 propensity score matching, the postoperative functional outcomes of 27 cases of RARP with PEEL and 27 cases of RARP with PPSS were compared. All surgeries were performed by a single surgeon and included patients were clinically staged as cT1-2N0M0 without preoperative urinary incontinence or erectile dysfunction. In RARP with PEEL, the prostate was cut near the midline at the front when dissecting the neurovascular bundle, dissection was performed between the visceral layer of the pelvic fascia and the prostatic fascia, preserving the parietal layer and the visceral layer of the pelvic fascia, and the neurovascular bundle was retrogradely released from the apex. The cumulative probability curve was plotted using the Kaplan-Meier method and the Log-rank test was used to compare the differences in functional outcomes between the two groups. Univariate and multivariate analysis with the Cox proportional hazards model was used to compare postoperative urinary continence and sexual function.Results:The recovery time of continence and potency was significantly longer in the PPSS group than in the PEEL group (all P<0.05). The continence rate of the PEEL group was significantly higher than that of the PPSS group (92.59% vs. 68.10%, P=0.026) at 3 months after surgery. The potency rate of the PEEL group was also significantly higher than that of the PPSS group (40.70% vs. 15.10%, P=0.037) at 3 months after surgery. In the univariate analysis, compared to the PPSS technique, the PEEL technique was associated with a shorter recovery time of continence ( HR=1.94, 95% CI: 1.08 to 3.48, P=0.027) and a shorter recovery time of potency ( HR=2.06, 95% CI: 1.03 to 4.13, P=0.042). In the multivariate analysis, the PEEL technique was an independent prognosis factor for postoperative recovery of continence ( HR=2.05, 95% CI: 1.01 to 4.17, P=0.047) and potency ( HR=3.57, 95% CI: 1.43 to 8.92, P=0.007). All the cases of the PPSS group and the PEEL group were performed successfully with negative surgical margins. Conclusion:Compared with PPSS, PEEL may be more conducive to the recovery of urinary continence and sexual function after RARP.

Objectives:To examine the functional outcomes of robot-assisted radical prostatectomy (RARP) with preservation of pelvic floor stabilized structure and early elevated retrograde liberation of the neurovascular bundle (PEEL).Methods:This study was a retrospective cohort study. Between June 1, 2022, and March 20, 2023, 27 cases of RARP with PEEL and 153 cases of RARP with preservation of pelvic floor stabilized structure (PPSS) were included in this study. All patients were males, aged (62.5±5.2) years (range: 50 to 73 years). There were 18 cases of ≤T2b stage and 9 cases of T2c stage. After 1∶1 propensity score matching, the postoperative functional outcomes of 27 cases of RARP with PEEL and 27 cases of RARP with PPSS were compared. All surgeries were performed by a single surgeon and included patients were clinically staged as cT1-2N0M0 without preoperative urinary incontinence or erectile dysfunction. In RARP with PEEL, the prostate was cut near the midline at the front when dissecting the neurovascular bundle, dissection was performed between the visceral layer of the pelvic fascia and the prostatic fascia, preserving the parietal layer and the visceral layer of the pelvic fascia, and the neurovascular bundle was retrogradely released from the apex. The cumulative probability curve was plotted using the Kaplan-Meier method and the Log-rank test was used to compare the differences in functional outcomes between the two groups. Univariate and multivariate analysis with the Cox proportional hazards model was used to compare postoperative urinary continence and sexual function.Results:The recovery time of continence and potency was significantly longer in the PPSS group than in the PEEL group (all P<0.05). The continence rate of the PEEL group was significantly higher than that of the PPSS group (92.59% vs. 68.10%, P=0.026) at 3 months after surgery. The potency rate of the PEEL group was also significantly higher than that of the PPSS group (40.70% vs. 15.10%, P=0.037) at 3 months after surgery. In the univariate analysis, compared to the PPSS technique, the PEEL technique was associated with a shorter recovery time of continence ( HR=1.94, 95% CI: 1.08 to 3.48, P=0.027) and a shorter recovery time of potency ( HR=2.06, 95% CI: 1.03 to 4.13, P=0.042). In the multivariate analysis, the PEEL technique was an independent prognosis factor for postoperative recovery of continence ( HR=2.05, 95% CI: 1.01 to 4.17, P=0.047) and potency ( HR=3.57, 95% CI: 1.43 to 8.92, P=0.007). All the cases of the PPSS group and the PEEL group were performed successfully with negative surgical margins. Conclusion:Compared with PPSS, PEEL may be more conducive to the recovery of urinary continence and sexual function after RARP.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective:To explore the optimal storage condition and time of umbilical cord blood from collection to preparation.Methods:Collect cord blood samples from 30 healthy newborns,with each new born's umbilical cord blood was divided into two parts on average.One part was stored in cold storage(4 ℃)and the other was stored at room temperature(20-24 ℃).Samples were taken at 24,36,48,60 and 72 h,respectively,total nucleated cells(TNC)count and TNC viability was analyzed.Flow cytometry was used to detect the ratio of viable CD34+cells to viable CD45+cells and viability of CD34+cells,and colony-forming unit-granulocyte-macrophage(CFU-GM)count was performed by hematopoietic progenitor cell colony culture.The change trend of each index over time was observed,and the differences in each index was compared between cold storage and room temperature storage under the same storage time.Results:The TNC count(r4℃=-0.9588,r20-24℃=-0.9790),TNC viability(r4℃=-0.9941,r20 24 ℃=-0.9970),CD34+cells viability(r4℃=-0.9932,r20-24℃=-0.9828)of cord blood stored in cold storage(4 ℃)and room temperature storage(20-24 ℃)showed a consistent downward trend with the prolongation of storage time.The percentage of viable CD34+cells(r4℃=0.9169,r20-24 ℃=0.7470)and CFU-GM count(r4℃=-0.2537,r20-24℃=-0.8098)did not show consistent trends.When the storage time was the same,the TNC count,TNC viability,CD34+cells viability and CFU-GM count of cord blood stored in cold storage were higher than those stored at room temperature.Under the same storage time(24,36,48,60 or 72 h),TNC viability in room temperature storage was significantly lower than that in cold storage(P＜0.001),but TNC count,percentage of viable CD34+cells and CFU-GM count were not significantly different between room temperature storage and cold storage.When stored at room temperature for 24 h and 36 h,the viability of CD34+cells was significantly lower than that in cold storage(P＜0.001,P＜0.01),when the storage time for 48,60 and 72 h,there was no significant difference in the CD34+cells viability between room temperature storage and cold storage.Conclusion:It is recommended that cord blood be stored in cold storage(4 ℃)from collection to preparation,and processed as soon as possible.

OBJECTIVE: To observe the effects of auricular thumbtack needle on breast feeding and lactation function in primiparous women with cesarean section, and to explore its mechanism of action from the perspective of lactation-related gene expression. METHODS: One hundred cases of primiparous women with cesarean section were randomly divided into an observation group (50 cases, 3 cases dropped off) and a control group (50 cases, 2 cases were eliminated). The patients in the control group were treated with routine obstetric care. Based on the treatment of the control group, the patients in the observation group were treated with auricular thumbtack needle at Neifenmi (CO₁₈), Xiong (AH₁₀), Xiongzhui (AH₁₁), Shenmen (TF₄), and Jiaogan (AH_6a), etc., with one side of auricular point selected, only once for a total of 3 d. The lactation initiation time, lactation adequacy rate at postpartum 72 h, exclusive breastfeeding rate at postpartum 42 d, and breastfeeding score after treatment were compared between the two groups. Real-time quantitative PCR and Western blot method were used to detect the mRNA and protein expression levels of TDP-43, Btn1A1 and XDH. RESULTS: After treatment, the lactation initiation time in the observation group was earlier than that in the control group (P<0.01), and breastfeeding score in the observation group was higher than that in the control group (P<0.01). The lactation adequacy rate at postpartum 72 h was 63.8% (30/47) in the observation group, which was higher than 41.7% (20/48) in the control group (P<0.05). The exclusive breastfeeding rate at postpartum 42 d was 72.3% (34/47) in the observation group, which was higher than 47.9% (23/48) in the control group (P<0.05). The mRNA and protein expression levels of TDP-43 and Btn1A1 in breast milk in the observation group were higher than those in the control group (P<0.01), while there was no statistically significant difference in mRNA and protein expression of XDH in breast milk between the two groups (P>0.05). CONCLUSION The auricular thumbtack needle in addition to routine care could promote lactation initiation, improve lactation adequacy rate and exclusive breastfeeding rate in primiparous women with cesarean section, and the action mechanism may be related to up-regulation of TDP-43 and Btn1A1 expression.
Pregnancy ; Humans ; Female ; Breast Feeding ; Cesarean Section ; Lactation ; Milk, Human ; DNA-Binding Proteins

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*