Estrogen receptor beta suppresses the androgen receptor oncogenic effects in triple-negative breast cancer / 中华医学杂志(英文版)

BACKGROUND@#Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. The androgen receptor (AR) has emerged as a potential therapeutic target for luminal androgen receptor (LAR) TNBC. However, multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits. This study aimed to investigate the role of AR in TNBC and its detailed mechanism.@*METHODS@#Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4 (NECTIN4) expression in TNBC tissues. Then, in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta (ERβ) in TNBC. Chromatin immunoprecipitation sequencing (ChIP-seq), co-immunoprecipitation (co-IP), molecular docking method, and luciferase reporter assay were performed to identify key molecules that affect the function of AR.@*RESULTS@#Based on the TNBC tissue array analysis, we revealed that ERβ and AR were positive in 21.92% (32/146) and 24.66% (36/146) of 146 TNBC samples, respectively, and about 13.70% (20/146) of TNBC patients were ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection in LAR TNBC cell lines but not in AR-negative TNBC. Mechanistically, we identified that NECTIN4 promoter -42 bp to -28 bp was an AR response element, and that ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial-mesenchymal transition in tumor progression.@*CONCLUSIONS@#This study suggests that ERβ functions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation. Therefore, our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

Effects of Yiqi Huoxue Tuodu Prescription on Keap1/Nrf2/HO-1 Signaling Pathway in Rats with Chronic Nonbacterial Prostatitis / 中国中医药信息杂志

Objective To observe the effects of Yiqi Huoxue Tuodu Prescription on Keap1Nrf2/HO-1 signaling pathway in rats with chronic nonbacterial prostatitis(CNP);To explore its mechanism for the treatment of CNP.Methods CNP rat model was prepared using castration combined with estrogen induction method.Totally 48 SD rats were divided into blank group,model group,celecoxib group and Yiqi Huoxue Tuodu Prescription group according to the random number table method,with 12 rats in each group.In the celecoxib group,celecoxib suspension was instilled 0.035 g/kg,and in the Yiqi Huoxue Tuodu Prescription group,Yiqi Huoxue Tuodu Prescription water decoction was instilled 8.64 g/kg,and the blank group and the model group were instilled with equal volume of normal saline for 28 days.Mechanical pain threshold in rats was measured using Von Frey fiber optic pain gauge,HE staining was used to observe pathological changes in prostate tissue and pathological scoring,the content of reactive oxygen species(ROS)in prostate tissue were detected by chemical fluorescence method and the glutathione peroxidase(GSH-Px)activity and malondialdehyde(MDA)content in prostate tissue were detected by colorimetric method,Western blot was used to detect the expressions of Kelch like ECH related protein 1(Keap1),nuclear factor E2 related factor 2(Nrf2),and heme oxygenase-1(HO-1)protein in prostate tissue.Results Compared with the blank group,rats in the model group had significantly lower mechanical pain threshold and significantly decreased prostate index(P<0.01);the size of the glandular cavity in prostate tissue varied,with the disappearance of secretions in the cavity,interstitial looseness and edema,a large amount of fibrous tissue hyperplasia and inflammatory cell infiltration,and a significant increase in pathological scores(P<0.01);the contents of ROS and MDA in prostate tissue significantly increased,the activity of GSH-Px significantly decreased(P<0.01),the expression of Keap1 and Nrf2 proteins significantly decreased,and the expression of HO-1 protein significantly increased(P<0.01,P<0.05).Compared with the model group,the mechanical pain threshold of the rats in the Yiqi Huoxue Tuodu Prescription group was significantly higher(P<0.01);there was mild damage to prostate tissue,with a small amount of fibrous hyperplasia and inflammatory cell infiltration,and a significant decrease in pathological scores(P<0.01,P<0.05);the contents of ROS and MDA in prostate tissue significantly decreased,and the GSH-Px activity significantly increased(P<0.01),the Keap1 and Nrf2 protein expressions significantly increased and HO-1 protein expression significantly decreased in prostate tissue(P<0.01,P<0.05).Conclusion Yiqi Huoxue Tuodu Prescription can effectively improve the histopathological morphology and increase the pain threshold of the prostate gland in CNP rats,and its mechanism of action may be related to the regulation of Keap1/Nrf2/HO-1 signaling pathway and reduction of oxidative stress damage in prostate tissue of rats.

Application of a self-designed pre-positioned 3D honeycomb guide device in internal fixation with percutaneous cannulated screws for treatment of femoral neck fractures / 中华创伤骨科杂志

Objective:To evaluate our self-designed pre-positioned 3D honeycomb guide device in the internal fixation with percutaneous cannulated screws for femoral neck fractures.Methods:A retrospective study was conducted to analyze the data of 60 patients with femoral neck fracture who had been treated with cannulated screw fixation at Department of Orthopaedics, Kunshan Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Traditional Chinese Medicine from June 2019 to June 2022. According to the difference in intraoperative positioning for placement of cannulated screws, the patients were divided into a study group of 30 cases whose placement of cannulated screws was assisted by our self-designed pre-positioned 3D honeycomb guide device, and a control group of 30 cases whose cannulated screws were positioned freehand. In the study group, there were 17 males and 13 females with an age of (44.9±9.2) years, and 2 cases of type Ⅱ, 18 cases of type Ⅲ, and 10 cases of type Ⅳ by the Garden classification. In the control group, there were 11 males and 19 females with an age of (43.5±7.9) years), and 1 case of type Ⅱ, 16 cases of type Ⅲ, and 13 cases of type Ⅳ by the Garden classification. Closed reduction and inverted triangle internal fixation with 3 cannulated screws were conducted for all fractures. The Garden crossline index, operation time, fluoroscopy frequency, needle drillings, fracture healing time, and Harris hip functional score at the last follow-up were compared between the 2 groups. The postoperative imaging indicators in the 2 groups were measured, including screw spacing, distance from screw to neck cortex, screw coverage area, parallel deviation between screws, and deviation from screw to neck axis.Results:There were no statistically significant differences in the baseline characteristics between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (14.4±1.9) months after surgery. In the study group, operation time [(33.1±5.5) min], fluoroscopy frequency [(13.7±2.2) times], needle drillings [(3.7±0.6) times], distance from screw to neck cortex [(12.4±2.8) mm], parallel deviation between screws in the anteroposterior view (2.2°±1.1°), parallel deviation between screws in the lateral view (2.4°±1.0°), deviation from screw to neck axis in the anteroposterior view (4.0°±0.9°) and deviation from screw to neck axis in the lateral view (3.2°±0.8°) were all significantly smaller than those in the control group [(46.5±8.6) min, (23.1±5.2) times, (11.0±2.2) times, (19.0±3.3) mm, 6.5°±2.6°, 7.1°±2.9°, 7.7°±2.6°, and 9.2°±3.1°] (all P<0.05). The screw spacing [(45.7±5.8) mm] and screw coverage area [(74.1±10.9) mm 2] in the study group were both significantly larger than those in the control group [(31.3±7.7) mm and (55.5±9.0) mm 2] ( P<0.05). There was no statistically significant difference between the 2 groups in Garden crossline index, fracture healing time, follow-up time, or Harris hip functional score at the last follow-up ( P>0.05). Follow-ups revealed 1 case of bone non-union in the study group and 2 cases of bone non-union and screw withdrawal in the control group, but no such complications as infection, deep vein thrombosis, screw penetration or rupture, or femoral head necrosis in either group. Conclusion:In the internal fixation with percutaneous cannulated screws for the treatment of femoral neck fractures, our self-designed pre-positioned 3D honeycomb guide device can shorten surgical time, significantly reduce fluoroscopy frequency and needle drillings, and effectively improve accuracy of screw placement.

Clinical application of 3D-printed drill guiding template in pedicle screw insertion in subaxial cervical spine / 中国脊柱脊髓杂志

Objectives:To explore the safety and accuracy of subaxial cervical pedicle screw(CPS)insertion assisted with optimized 3D-printed drill guiding template(DGT).Methods:A retrospective study was conducted to analyze the clinical data of 42 patients aged 32-74 years(50.1±9.8 years)who underwent posterior cervi-cal pedicle screw intemal fixation between August 2016 and October 2022.The patients were followed up for 13-25 months(19.6±3.2 months).They were divided into two groups of guiding template group(n=22)and free-hand group(n=20)according to the method of pedicle screw insertion.In the guiding template group,the sub-axial CPSs insertions were assisted with 3D-printed DGT,designed individually for each patient based on the design scheme of an optimized pedicle drill guiding template,and the patients consisted of 12 males and 10 females,among which 6 patients were with cervical spine injury or spinal cord injury,9 were with ossifica-tion of posterior longitudinal ligament(OPLL),5 were with intraspinal tumor,and 2 were with cervical spondy-lotic myelopathy.In the free-hand group,the subaxial CPSs were inserted with free hand according to the cervical parameters such as pedicle angle and diameter on the CT images measured before operation,and the patients consisted of 10 males and 10 females,among which 4 patients were with cervical spine injury or spinal cord injury,10 with OPLL,5 with intraspinal tumor,and 1 with cervical spondylotic myelopathy.There were no significant differences in sex,age,disease,and preoperative visual analogue scale(VAS)score and Japanese Orthopaedic Association(JO A)score between the two groups(P＞0.05).The operative time,intraopera-tive blood loss,and postoperative 12 months of VAS and JOA scores were recorded and compared.CT scan was performed at 1 week after operation on cervical spine,and the accuracy of pedicle screw placement was evaluated in accordance with Kaneyama's evaluation method:Grade 0,screw was contained in the pedicle;Grade 1,screw penetrated pedicle＜50％of the screw diameter;Grade 2,screw penetrated pedicle＞50％of the screw diameter;Grade 3,screw completely penetrated the pedicle.Grades 0 and 1 were considered accurate placement,and grades 2 and 3 were considered misplacement.The perioperative complications were recorded for each patient in the two groups.Results:The operative time,intra-operative blood loss in guiding template group(102.2±16.1min,89.3±17.7mL)were statistically less than those in free-hand group(142.8±20.9min,133.3±34.0mL)(P＜0.01).A total of 216 CPSs were placed:118 in the guiding template group,including 90 screws of grade 0,22 screws of grade 1,5 screws of grade 2,1 screw of grade 3,with an accuracy rate of 94.9％(112/118);And 98 in the free-hand group,including 48 screws of grade 0,36 screws of grade 1,10 screws of grade 2,and 4 screws of grade 3,with an accuracy rate of 85.7％(84/98).The accuracy rate of pedicle screw insertion was significant higher in the guiding template group than that in the free-hand group(P＜0.05).No major neurovascular complications nor internal fixation loosening or breakages were observed in two groups of patients.At 12 months after operation,the VAS score in both groups was statistically less than that before operation(P＜0.01),and the JOA score in both groups was statistically more than that before opera-tion(P＜0.01),and there were no significant differences in VAS score and JOA score between groups,respec-tively(P＞0.05).Conclusions:The optimized design scheme of 3D-printed DGT is helpful in improving the ac-curacy and safety of subaxial CPS insertion.

Improvement effect of diterpene ginkgolides on acute tMCAO rats and chronic tMCAO rats / 药学学报

To study the cognitive effects of diterpene ginkgolides (DG), transient middle cerebral artery occlusion (tMCAO)-induced rats were established. tMCAO-rats induced by suture method were divided into sham operation group, solvent control group, NBP group, DG group. The animal experiments in the present study were performed in accordance with the Ethical Guidelines of the Laboratory Animal Welfare Ethical Committee of Peking Union Medical College (00000646, 00000635). The effects of DG on tMCAO rats were evaluated by neurological severity score, cerebral infarction volume measurement, step-down and Morris water maze test. In the acute tMCAO rat model, 100 mg·kg-1 DG improved the neural score and infarction volume. In the chronic tMCAO rat model, DG 100 mg·kg-1 significantly improved the survival rate of tMCAO-induced rats. The Morris water maze results showed 100 mg·kg-1 DG decreased the latency of tMCAO-induced rats to find the platform, while the effect was weaker than the NBP. However, DG 30 mg·kg-1 did not show a significant effect. In conclusion, DG exerted a therapeutic effect on transient middle cerebral artery occlusion.

Clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm accelerated/blast phase / 中华血液学杂志

Objective: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase (MPN-AP/BP) . Methods: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. Results: ① Sixty-seven patients with MPN-AP/BP with a median age of 60 (range, 33-75) years, including 31 males (46.3% ) and 36 females (53.7% ) , were analyzed. Forty-eight patients progressed from primary myelofibrosis (PMF) , and 19 progressed from other myeloproliferative neoplasms (MPNs) , which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase (LDH) levels than those who progressed from other MPNs (925.95 vs. 576.2 U/L, P=0.011) , and there were higher proportions of patients who progressed from PMF with splenomegaly (81.4% vs. 57.9% , P=0.05) , a myelofibrosis grade of ≥2 (93.6% vs. 63.2% , P=0.004) , and a shorter duration from diagnosis to the transformation to AP/BP (28.7 vs. 81 months, P=0.001) . ② JAK2V617F, CALR, and MPLW515 were detected in 41 (61.2% ) , 13 (19.4% ) , and 3 (4.5% ) patients, respectively, whereas 10 (14.9% ) patients did not have any driver mutations (triple-negative) . Other than driver mutations, the most frequently mutated genes were ASXL1 (42.2% , n=27) , SRSF2 (25% , n=16) , SETBP1 (22.6% , n=15) , TET2 (20.3% , n=13) , RUNX1 (20.3% , n=13) , and TP53 (17.2% , n=11) . The ASXL1 mutation was more enriched (51.1% vs. 21.1% , P=0.03) , and the median variant allele fraction (VAF) of the SRSF2 mutation (median VAF, 48.8% vs. 39.6% ; P=0.008) was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype (hazard ratio, 2.53; 95% confidence interval, 1.06-6.05; P=0.036) was independently associated with worse overall survival (OS) . Patients who received allogeneic stem cell transplantation (allo-HSCT) (median OS, 21.3 vs. 3 months; P=0.05) or acute myeloid leukemia-like (AML-like) therapy (median OS, 13 vs. 3 months; P=0.011) had significantly better OS than those who received supportive therapy. Conclusion: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.

Effectiveness of comprehensive intervention on primary dental caries in 3-year-old children in Bengbu / 中国学校卫生

Objective@#To explore the effectiveness of the comprehensive intervention on prevention of deciduous primary caries in 3-year-old children, so as so provide reference for the prevention, health care and treatment of oral caries.@*Methods@#Three-year-old children selected by drawing lots from 10 public kindergartens in 5 districts of Bengbu were examined in 2021, and were randomly divided into intervention group ( n =300) and control group ( n =300). During the initial examination, caries loss (dmf) including dental caries, missing teeth, filling teeth were assessed in the two groups. At the initial examination, the intervention group received caries intervention while no intervention was administered in the non-intervention group until half a year later. Intervention measures included education, diet, self-cleaning and fluoride application intervention. The number of cases and the mean of caries loss in the two groups were compared by χ 2 test.@*Results@#Before the intervention, 43 children in the control group suffered from caries, with 88 dmf, including 44 dmf for boys and 44 dmf for girls. There were 45 children in the intervention group, with 101 dmf, including 49 dmf for boys and 52 dmf for girls. There was no significant difference in the number of dmf between the intervention group and the control group ( χ 2=0.91, P >0.05), and there was no significant difference in the prevalence rate (15.0%, 14.3%, χ 2=0.05, P >0.05). After the intervention, there were 26 new dental caries and 43 dmf in intervention group, including 25 dmf for boys and 18 dmf for girls. In the control group, there were 83 new dental caries and 168 dmf, including 72 dmf for boys and 96 dmf for girls. Compared with the control group, the new dmf in the intervention group was significantly different ( χ 2=75.38, P < 0.05). The number of new dental caries patients in the intervention group was significantly different from that in the control group ( χ 2=36.42, P <0.05).@*Conclusion@#Comprehensive interventions to prevent dental caries can significantly reduce the incidence of primary teeth caries in children. It is suggested to intervene dental caries as early as possible to reduce the incidence of dental caries and other oral diseases.

Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF) / 中华内科杂志

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

Analysis of risk factors of mortality in infants and toddlers with moderate to severe pediatric acute respiratory distress syndrome / 中华儿科杂志

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ2=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ2=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ2=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.

Efficacy and safety of ceftazidime and avibactam sodium in the treatment of carbapenem-resistant organism infection / 中国药房

OBJECTIVE To observe the efficacy and safety of ceftazidime and avibactam sodium （CAZ/AVI） in the treatment of carbapenem-resistant organism （CRO） infection. METHODS The information of patients with CRO infection admitted to the Second Affiliated Hospital of Soochow University from September 2019 to March 2022 was collected， and the patients were retrospectively divided into observation group （48 cases） and control group （48 cases） according to the treatment plan. The control group was given Polycolistin B sulfate for injection intravenously at a dose of 500 000 U every 12 hours； no dose adjustment was performed in patients with renal insufficiency or receiving continuous renal replacement therapy （CRRT）. The observation group was given continuous micropump of CAZ/AVI for injection intravenously at a dose of 2.5 g every 8 hours for 2 continous hours； among them， the patients with renal insufficiency received an adjusted dose based on creatinine clearance， and no dose adjustment was performed in patients receiving CRRT. The clinical efficacy and microbiological efficacy as well as body temperature， white blood cell （WBC）， C-reactive protein （CRP） and procalcitonin （PCT） before and after treatment were compared between 2 groups. The prognosis and the occurrence of adverse drug reactions were recorded. The factors influencing the clinical efficacy were screened by Logistic regression analysis. RESULTS The effective rate and microbial clearance rate of the observation group were significantly higher than the control group （P＜0.05）. After treatment， body temperature， PCT and CRP of 2 groups were significantly lower than before treatment， and CRP of the observation group was significantly lower than the control （No.SDFEYJLC2105） group （P＜0.05）. There was no statistically significant differencebetween the two groups in terms of rehabilitation discharge rate， the proportion of patients transferred to general wards，the proportion of dead patients， and the total incidence ofadverse drug reactions （P＞0.05）. CAZ/AVI and prolonging therapy duration were more likely to achieve clinical benefits （odds ratios of 1.146， 7.707，P＜0.05）， while lung infection and CRRT may be independent risk factors for treatment failure （odds ratios of 0.182， 0.236， P＜0.05）. CONCLUSIONS CAZ/AVI has good efficacy and safety in the treatment of CRO infection， the appropriate extension of antibacterial treatment time can achieve a higher clinical response rate， while lung infection or CRRT may lead to treatment failure.

Immune-Related Pancreatitis Caused by Immune Checkpoint Inhibitor Nivolumab:Report of One Case / 中国医学科学院学报

In recent years,great progress has been achieved in the application of immune checkpoint inhibitors (ICI) in tumor immunotherapy.However,a variety of adverse reactions induced by ICI have been reported.Despite the high overall incidence of adverse reactions caused by ICI,some adverse reactions,such as immune-related pancreatitis,are rare in clinical practice.In this paper,a case of immune-related pancreatitis after treatment of advanced gastric cancer with nivolumab was identified.We analyzed the cause,treatment,incidence,and risk factors of the adverse reaction,aiming to improve the clinical diagnosis,treatment,and safe medication of rare adverse reactions associated with ICI.

To explore the quality markers of Huangqin Qingre Chubi capsule in the treatment of rheumatoid arthritis based on network pharmacology combined with pharmacokinetics and target verification / 药学学报

As an effective prescription for the treatment of rheumatoid arthritis (RA), Huangqin Qingre Chubi capsule (HQC) is still blank in quality control. This study aims to explore quality markers (Q-markers) for HQC in the treatment of RA by integrating network pharmacology and pharmacokinetics. By constructing the visualization network of "pharmacodynamic ingredient-target-pathway", the potential Q-Marker of HQC treatment for RA was preliminatively predicted. A rat model of rheumatic heat obstruction syndrome collagene-induced arthritis (CIA) was established to elucidate the dynamic quantification law of pharmacodynamic components of HQC in the disease state of rats. To establish the inflammatory model of RA synovial fibroblasts (MH7A) induced by tumor necrosis factor-α (TNF-α) in vitro. The effects of active ingredients on protein expression of sphingosin kinase-1 (Sphk1) and p-SphK1 were detected. The network pharmacological results showed that baicalin, geniposide, luteolin, coixol and amygdalin were the important active components of HQC treatment for RA. Quantitative analysis results further verified the measurability of these five components. The expression of Sphk1 and p-SphK1 was significantly inhibited by geniposide and baicalin by Western blotting. The above studies determined that the above 5 components could be used as Q-markers in the treatment of RA by HQC. This experiment was approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-rats-2021049). All procedures were conducted in strict accordance with the principles of animal use and care.

The influence of family structure on depression and anxiety symptoms in adolescents: the mediating role of emotional neglect / 中国当代儿科杂志

OBJECTIVES@#To study the influence of family structure on depression and anxiety symptoms in adolescents and its mechanism.@*METHODS@#The cluster sampling method was used to select the students from seven middle schools in Shanghai, China. An online questionnaire survey was conducted using a self-made general status questionnaire, Childhood Trauma Questionnaire, Children's Depression Inventory, and Screen for Child Anxiety Related Emotional Disorders. The methods including one-way analysis of variance, chi-square test, binary logistic regression analysis, and mediating effect analysis were used to evaluate depression and anxiety symptoms in adolescents and the difference in childhood trauma and its mediating effect.@*RESULTS@#Compared with the adolescents from nuclear families, the adolescents from three-generation lineal families had a lower risk of depression symptoms (OR=0.794, 95%CI: 0.649-0.972, P<0.05), while those from host families had a higher risk of depression symptoms (OR=4.548, 95%CI: 1.113-18.580, P<0.05). The adolescents from inter-generational families and host families had a significantly higher score on the Childhood Trauma Questionnaire subscale of emotional neglect (P<0.05). Emotional neglect played a mediating role in the influence of inter-generational families and host families on depression symptoms in adolescents.@*CONCLUSIONS@#Parents and grandparents have a certain positive effect in family structures. Separation from parents may make adolescents perceive more emotional neglect, which may increase the occurrence of depression symptoms.

Association between maternal job burnout and adolescent depression: the chain mediating effect of maternal depression and parenting style / 中国当代儿科杂志

OBJECTIVES@#To investigate the association between maternal job burnout and adolescent depression and the mediating effect of maternal depression and parenting style.@*METHODS@#A cross-sectional study was conducted. The cluster random sampling method was used to select 2 572 adolescents from 7 middle schools in Shanghai, China, from April to May, 2021. A survey was performed for these adolescents and their mothers. The research tools included a general information questionnaire, Maslach Burnout Inventory-General Survey, Center for Epidemiologic Studies Depression Scale, short-form of Egna Minnen av Barndoms Uppfostran, and Children's Depression Inventory. A structural equation model was established, and the Bootstrap method was used to investigate the mediating effect.@*RESULTS@#The detection rate of depressive symptoms was 12.71% (327/2 572) among the adolescents. The scores of maternal job burnout, maternal depression, and negative parenting style were positively correlated with the score of adolescent depression (P<0.05), and the score of positive parenting style was negatively correlated with the score of adolescent depression (P<0.05). Maternal depression and parenting style played a mediating role between maternal job burnout and adolescent depression, including the individual mediating effect of maternal depression, the individual mediating effect of positive parenting style, and the chain mediating effect of maternal depression-negative/positive parenting style.@*CONCLUSIONS@#Maternal job burnout may affect adolescent depression through the mediating effect of depression, parenting style, and depression-parenting style, suggesting that the symptoms of adolescent depression can be reduced by alleviating maternal job burnout, improving maternal depression, increasing positive parenting behaviors, and reducing negative parenting behaviors.

Chromatin Remodeling Factor SMARCA5 is Essential for Hippocampal Memory Maintenance via Metabolic Pathways in Mice / 神经科学通报·英文版

Gene transcription and new protein synthesis regulated by epigenetics play integral roles in the formation of new memories. However, as an important part of epigenetics, the function of chromatin remodeling in learning and memory has been less studied. Here, we showed that SMARCA5 (SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 5), a critical chromatin remodeler, was responsible for hippocampus-dependent memory maintenance and neurogenesis. Using proteomics analysis, we found protein expression changes in the hippocampal dentate gyrus (DG) after the knockdown of SMARCA5 during contextual fear conditioning (CFC) memory maintenance in mice. Moreover, SMARCA5 was revealed to participate in CFC memory maintenance via modulating the proteins of metabolic pathways such as nucleoside diphosphate kinase-3 (NME3) and aminoacylase 1 (ACY1). This work is the first to describe the role of SMARCA5 in memory maintenance and to demonstrate the involvement of metabolic pathways regulated by SMARCA5 in learning and memory.

Analysis of disease spectrum for abnormal 3-hydroxyisovalerylcarnitine metabolism identified through newborn screening and clinical diagnosis / 中华医学遗传学杂志

OBJECTIVE@#To explore the disease spectrum for abnormal 3-hydroxyisovalerylcarnitine (C5OH) metabolism identified through newborn screening and clinical diagnosis patients and the key points for differential diagnosis so as to raise the awareness of pediatricians for such diseases.@*METHODS@#Clinical data of 85 neonates with abnormal C5OH metabolism identified from February 2004 to January 2022 at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were collected. Their clinical manifestations and results of tandem mass spectrometry (MS/MS), gas chromatography mass spectrometry (GC-MS) and genetic testing were retrospectively analyzed.@*RESULTS@#Among the 85 cases, 46 (54.1%) were identified by neonate screening, whilst 39 (45.9%) were clinically diagnosed patients. Five diseases were diagnosed, including 28 cases with multiple carboxylase deficiency (MCD, 32.9%), 29 cases with 3-methylcrotonyl-coenzymeAcarboxylasedeficiency (MCCD, 34.1%), 4 cases with 3-methylglutaconic acid (3-MGA, 4.7%), 7 cases with 3-hydroxy-3-methylglutaric acid (3-HMG, 8.2%), and 17 cases with beta-ketothiolase deficiency (BKD, 20.0%). The disorders were characterized by sudden onset, anorexia, vomiting, diarrhea, abnormal breathing, consciousness disorder, spasm and developmental delay.@*CONCLUSION@#Among newborns with abnormal C5OH metabolism, MCCD is the most common disorder, which was followed by BKD and MCD. For patients with abnormal C5OH metabolism, MCD is the most common, followed by BKD and 3-HMG. C5OH related diseases have great heterogeneity. Combination of blood acylcarnitine levels, urinary organic acid levels and genetic testing based on clinical characteristics can help to attain the diagnosis.

Efficacy of Jiangsha Banxia nano-paste on nausea and vomiting in end-stage patients and its effect on QOL in cancer patients / 药学实践与服务

Objective To observe the clinical efficacy of Jiangshabanxia nano-paste on nausea and vomiting in end-stage patients and its effect on the quality-of-life (QOL) in cancer patients. Methods 120 end-stage patients with nausea and vomiting symptoms above grade III were randomly divided into observation group and control group. They were treated with Jiangshabanxia nano-paste and placebo paste respectively. The paste patch was changed every 24 hours and used continuously for 7 days. The nausea and vomiting symptom score, the quality-of-life measurement score and KPS score of cancer patients in the two groups were observed to evaluate the curative effect. Results After 7 days of treatment, the symptom scores of nausea and vomiting in the observation group decreased significantly, the KPS score of the observation group increased, and the effective rate was higher than that in the control group. The score of QOL measurement showed that after treatment, the score of main symptom areas and other symptom areas (except external dyspnea, diarrhea and economic difficulties) in the observation group decreased, and the score of overall health area increased. After treatment, the score of main symptom areas and other symptom areas (except external dyspnea, diarrhea and economic difficulties) in the observation group was lower than that in the control group, and the scores of overall health area in the observation group were higher than those in the control group. Conclusion Jiangshabanxia nano-paste has a good clinical efficacy nausea and vomiting in end-stage patients, it also can improve the quality of life end-stage cancer patients.

Progress in clinical diagnosis and treatment of tracheoesophageal fistulas / 解放军医学杂志

Tracheoesophageal fistulas(TEF)is a kind of pathological fistula between trachea or bronchus and esophagus,including tracheoesophageal fistula and bronchoesophageal fistula.In clinical practice,tracheoesophageal-fistula is more often seen.There are many pathogenesis of TEF,which could cause serious complications.It is a disease which has serious impact on the quality of life,difficult to treat and high mortality.There are many methods to treat TEF,but the therapeutic effect is poor.There is an urgent need for new treatment methods to TEF.The detection of nasogastric tube retention by chest and abdominal X-ray is the gold standard for diagnosis.The main treatment methods include surgical treatment,stent implantation,local biological glue blocking,stem cell therapy and so on.In order to provide reference for relevant clinical diagnosis and treatment of TEF,this article reviews the main research progress in the diagnosis and treatment of TEF in recent years.

Construction of a medical data security system based on domestic cloud native technology / 现代医院

Medical data involves patients'privacy and is an important factor in the healthcare of our nation's people.However,in recent years,with a serious of development trends such as mobile office and cloud-based storage of medical data,the risk of data leakage has further increased.In order to effectively deal with this phenomenon and ensure the security of patients'medical data to the greatest extent,Shantou Central Hospital has established a medical data security system in both managerial and technological dimensions through domestic Cloud Native technology to achieve the security control of the total life-cycle of data,providing a practical application-level solution for the construction of a systematic data security system.

Effects of sodium-glucose cotransporter 2 inhibitor dapagliflozin on myocardial remodeling in mice with diabetic cardiomyopathy / 中华老年医学杂志

Objective:To investigate the effects of sodium-glucose cotransporter 2 inhibitor dapagliflozin on myocardial remodeling in mice with diabetic cardiomyopathy and related mechanisms.Methods:Between January and December 2021, 60 6-week-old male C57BL/6J mice were chosen for the study, 40 were used to establish a diabetic cardiomyopathy model and the model was established in 28 mice, of whom, 14 were assigned to a non-intervention group and 14 to a dapagliflozin treatment group(intervention group).The rest of the 20 mice were in the control group.The mice in the intervention group were treated with dapagliflozin via oral gavage for 12 weeks.Cardiac structure and function were measured by ultrasound, the degree of myocardial fibrosis was evaluated by histology and electron microscopy, the concentrations of inflammatory factors were detected by enzyme-linked immunosorbent assays, apoptosis of myocardial cells was examined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL), and the level of myocardial oxidative stress was evaluated by dihydroethidium fluorescence.Results:At the end of the experiments, the body weight and fasting blood glucose in the intervention group were slightly lower than in the non-intervention group, but the difference was not statistically significant, while values from cardiac function parameters such as left ventricular ejection fraction were more favorable than in the non-intervention group[(61.07±4.66)% vs.(45.8±4.80)%, t=-5.24, P<0.05].Compared with the non-intervention group, the intervention group had alleviated myocardial hypertrophy, less myocardial disarray, and reduced collagen volume fraction[(18.4±1.9)% vs.(31.8±3.7)%, t=-12.0, P<0.05].Furthermore, the concentrations of inflammatory factors in the intervention group were lower than in the control group[interleukin-6: (82.19±10.90)ng/L vs.(291.02±31.02)ng/L, t=23.8, P<0.05; tumor necrosis factor-α: (70.45±12.13)ng/L vs.(201.31±27.10)ng/L( t=16.5), P<0.05; perforin 3: (13.05±2.04)μg/L vs.(42.40±1.26)μg/L( t=45.8), P<0.05; the index of myocardial apoptosis: 1.736±0.247 vs.0.864±0.129, t=11.7, P<0.05].The level of myocardial oxidative stress in the non-intervention group was higher than in the intervention group(2.655±0.252 vs.1.274±0.298, t=-13.3, P<0.05). Conclusions:Dapagliflozin can reduce myocardial hypertrophy and inhibit myocardial fibrosis through mitigating myocardial oxidative stress and inflammatory response, thus suppressing myocardial remodeling and ultimately protecting cardiac function in diabetic cardiomyopathy mice.