BACKGROUND: Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage. METHODS: A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate. RESULTS: In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes ( BRCA ) mutations ( BRCA m) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs . 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs . 91.4% (32/35), P <0.001]. The 24-month progression-free survival (PFS) rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCA m, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively. CONCLUSIONS Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCA m, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.
Humans ; Female ; Ovarian Neoplasms/drug therapy* ; Piperazines/therapeutic use* ; Middle Aged ; Retrospective Studies ; Phthalazines/therapeutic use* ; Piperidines/therapeutic use* ; Indazoles/therapeutic use* ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Adult ; Aged ; China ; Neoplasm Recurrence, Local/drug therapy* ; Progression-Free Survival

Objective To investigate the effect and mechanisms of celecoxib on right heart function in mice with acute high-altitude hypoxia exposure.Methods Male C57BL/6J mice(7 weeks old)were housed in a hypobaric chamber simulating an altitude of 5 800 m for 2 d to establish an animal model of acute hypobaric hypoxia.①Eighteen mice were randomly assigned to plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S),and high-altitude hypoxia exposure+celecoxib(H+Cel).Body weight and routine blood indicators were measured,and cardiac ultrasound examination were performed for heart rate(HR),pulmonary artery acceleration time to ejection time ratio(AT/ET),tricuspid annular plane systolic excursion(TAPSE),tricuspid annular systolic velocity(S'),and left ventricular ejection fraction(LVEF)and fractional shortening(FS).Targeted metabolomic profiling was applied to detect the cardiac arachidonic acid(AA)metabolite levels.The contents of 12,13-dihydroxy-9Z-octadecenoic acid(12,13-diHOME)in the heart,liver,brown adipose tissue,and plasma were quantified by ELISA.② Eighteen mice were randomly assigned into plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S)and high-altitude hypoxia exposure+12,13-diHOME(H+di)groups.Body weight,routine blood tests,and echocardiography were performed as above.③ Thirty-two mice were randomly divided into high-altitude hypoxia exposure+saline(H+S),high-altitude hypoxia exposure+celecoxib(H+Cel),high-altitude hypoxia exposure+soluble epoxide hydrolase inhibitor(sEHI)(H+sEHI),and high-altitude hypoxia exposure+sEHI+celecoxib(H+sEHI+Cel)groups.Body weight,routine blood tests,and echocardiography were performed as above.Cardiac and plasma contents of 12,13-diHOME and epoxyeicosatrienoic acids(EETs)were measured by ELISA.Results ① Compared to the P+S group,the H+S group exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.001),increased counts of white blood cells(WBC)and neutrophils(P<0.01)and decreased TAPSE,S'and AT/ET both at resting state and under stress(P<0.01,P<0.001).Compared to the H+S group,the H+Cel group exhibited significantly increase of cardiac 12,13-diHOME level(P<0.05),reduced WBC and lymphocyte counts(P<0.01,P<0.05)and improved TAPSE and S'levels at resting state and under stress(P<0.01,P<0.001).② Compared to the H+S group,the H+di group demonstrated significantly improvement of TAPSE at basal and under stress(P<0.001)and a trend towards improved TAPSE at resting state(P=0.0532),but no obvious differences was observed in WBC and neutrophil counts between the H+di group and the H+S group.③ Compared to the H+Cel group,both the H+sEHI and H+sEHI+Cel groups exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.01,P<0.05)though no statistical changes in cardiac function indicators.Compared to the H+S group,WBC counts and lymphocyte were decreased,and serum EETs level was incrased in the H+Cel group,H+sEHI group and H+sEHI+Cel group(P<0.01,P<0.001).Conclusion Celecoxib can elevate cardiac level of 12,13-diHOME and improves right heart function in mice after acute high-altitude hypoxia exposure through the CYP450-sEH metabolic pathway.

ObjectiveTo observe the effect of deep muscle stimulation on muscle structure and function in children with spastic cerebral palsy. MethodsFrom January, 2023 to March, 2024, 30 children with spastic cerebral palsy in Beijing Bo'ai Hospital were randomly divided into control group (n = 15) and intervention group (n = 15). Both groups received conventional rehabilitation therapy, while the intervention group added deep muscle stimulation, for four weeks. Before and after training, the gastrocnemius muscle was examined by ultrasound diagnosis system in two aspects: transverse incision and longitudinal incision. Indicators included fascicle length, muscular thickness, cross sectional area and pennation angle. The modified Ashworth Scale (MAS) was used to assess the muscle tension of the lower extremity of the affected side. The standing, walking, running and jumping function were evaluated by Gross Motor Function Measure (GMFM) D and E areas. ResultsAfter training, the fascicule length and pennation angle improved significantly in both groups (|t| > 6.329, P < 0.001), and they were better in the intervention group than in the control group (|t| > 2.347, P < 0.05); the scores of MAS decreased in both groups (t > 2.432, P < 0.05), and were better in the intervention group than in the control group (t = 2.140, P < 0.05); the scores of GMFM D and E areas significantly decreased in both groups (|t| > 8.473, P < 0.001), and were better in the intervention group than in the control group (|t| > 2.191, P < 0.05). ConclusionDeep muscle stimulation could improve the fascicule length and pennation angle, and improve the spasticity and motor function of lower extremities in children with spastic cerebral palsy.

Objectives:To investigate the early related factors for hepatic insufficiency after hemihepatectomy and to construct and validate a nomogram model.Methods:This is a retrospective cohort study.There were 207 patients with liver tumor who underwent hemihepatectomy in the Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to December 2022. Using the random number method, patients were randomly divided into a model group( n=166) and a validation group( n=41) according to an 4∶1 ratio. There were 118 males and 48 females in the modeling group,with an age ( M(IQR)) of 59.0(13.3) years (range: 22.0 to 81.0 years),42 patients in the group with postoperative liver insufficiency and 124 patients in the group without postoperative liver insufficiency. There were 32 males and 9 females in the validation group, with an age of 54.0(19.0) years (range: 25.0 to 81.0 years). The first results of the peripheral blood test of patients within 24 hours after surgery were collected,and the independent related factors for incomplete postoperative liver function were determined by multivariate Logistic regression analysis,and related factors of postoperative incomplete liver function were screened by best subset selection. A nomogram model of the related factors of postoperative hepatic insufficiency after hemihepatectomy was constructed using R software,validated by internal and external validation of the model. Results:Multivariate logistic regression analysis showed that elevated D-dimer level and decreased antithrombin Ⅲ (AT-Ⅲ) activity within 24 hours after surgery were independent related factors for the development of postoperative hepatic insufficiency in hemihepatectomized patients. The results of the best subset selection showed that ALT, D-dimer, and AT-Ⅲ activity levels within 24 hours postoperatively were the most relevant factors for postoperative hepatic insufficiency. The R software was applied to build a nomogram prediction model based on the above three indicators in the model set, and the receiver operating characteristic(ROC) curve of the model showed an area under the curve of 0.803 and the calibration curve showed a U-index of -0.012 for the model( P=0.977). The results of the clinical decision analysis and the clinical impact curve indicated that the model had good clinical utility. The internal validation results of the Bootstrap method suggested that the model had reasonable consistency. The area under the ROC curve of the validation group model was 0.806, suggesting that the model had a good generalization prediction ability. Conclusions:The levels of ALT, D-dimer, and AT-Ⅲ activity within 24 hours after hemihepatectomy are valuable indicators for predicting liver insufficiency after hemihepatectomy. The nomogram model is reliable and can be used as an indicator for close postoperative monitoring.

Objectives:To investigate the early related factors for hepatic insufficiency after hemihepatectomy and to construct and validate a nomogram model.Methods:This is a retrospective cohort study.There were 207 patients with liver tumor who underwent hemihepatectomy in the Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to December 2022. Using the random number method, patients were randomly divided into a model group( n=166) and a validation group( n=41) according to an 4∶1 ratio. There were 118 males and 48 females in the modeling group,with an age ( M(IQR)) of 59.0(13.3) years (range: 22.0 to 81.0 years),42 patients in the group with postoperative liver insufficiency and 124 patients in the group without postoperative liver insufficiency. There were 32 males and 9 females in the validation group, with an age of 54.0(19.0) years (range: 25.0 to 81.0 years). The first results of the peripheral blood test of patients within 24 hours after surgery were collected,and the independent related factors for incomplete postoperative liver function were determined by multivariate Logistic regression analysis,and related factors of postoperative incomplete liver function were screened by best subset selection. A nomogram model of the related factors of postoperative hepatic insufficiency after hemihepatectomy was constructed using R software,validated by internal and external validation of the model. Results:Multivariate logistic regression analysis showed that elevated D-dimer level and decreased antithrombin Ⅲ (AT-Ⅲ) activity within 24 hours after surgery were independent related factors for the development of postoperative hepatic insufficiency in hemihepatectomized patients. The results of the best subset selection showed that ALT, D-dimer, and AT-Ⅲ activity levels within 24 hours postoperatively were the most relevant factors for postoperative hepatic insufficiency. The R software was applied to build a nomogram prediction model based on the above three indicators in the model set, and the receiver operating characteristic(ROC) curve of the model showed an area under the curve of 0.803 and the calibration curve showed a U-index of -0.012 for the model( P=0.977). The results of the clinical decision analysis and the clinical impact curve indicated that the model had good clinical utility. The internal validation results of the Bootstrap method suggested that the model had reasonable consistency. The area under the ROC curve of the validation group model was 0.806, suggesting that the model had a good generalization prediction ability. Conclusions:The levels of ALT, D-dimer, and AT-Ⅲ activity within 24 hours after hemihepatectomy are valuable indicators for predicting liver insufficiency after hemihepatectomy. The nomogram model is reliable and can be used as an indicator for close postoperative monitoring.

Immune checkpoint inhibitors have significantly improved the prognosis of patients with mela-noma,but primary and acquired resistance have led to a bottleneck in treatment.The binding of T-cell receptors to tumor antigens is the key point for immunotherapy.Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations.Neoantigens,identifiable as foreign entities,have the capacity to initiate an immune response unfettered by central and peripheral tolerance mechanisms.This distinctive characteristic renders them highly promising targets in the realm of cancer therapy.Vaccines targeting tumor neoantigens,adoptive cell transfer,and antibody-based therapies can effectively enhance and expand tumor-specific immune responses,promoting T-cell recognition and elimination of tumors,thereby breaking through current treatment bottlenecks.This article discusses the current status,recent advancements,clinical challenges,and future direc-tions in the personalized treatment of melanoma based on neoantigens.

Objective For more focused prevention and management,this investigation examines the risk factors for multidrug resistant organisms(MDRO)infections in intensive care unit(ICU)patients.Methods Case-control studies and cohort studies of risk factors for MDRO infection in ICU patients were searched in the Embase,Website of Science,Cochrane Library,PubMed,CNKI,WanFang,and VIP databases from their start to October 26,2022.The Meta-analysis was carried out with RevMan 5.3.Results A total of 32 papers were included,with 10 985 cases studied,with the quality of the literature rated as moderate to high.The results of Meta-analysis of this study showed that gender[OR=1.21,95% CI=(1.08,1.36),P=0.002],ICU length of stay[WMD=5.36,95% CI=(3.99,6.73),P<0.000 01],total length of stay[WMD=8.96,95% CI=(6.51,11.41),P<0.000 01],hypertension[OR=1.33,95% CI=(1.10,1.60),P=0.003],abnormal renal function[OR=1.69,95% CI=(1.33,2.16),P<0.000 01],hypoproteinemia[OR=1.87,95% CI=(1.51,2.32),P<0.000 01],mechanical ventilation[OR=2.26,95% CI=(1.18,4.33),P=0.01],duration of mechanical ventilation[WMD=8.83,95% CI=(2.52,15.14),P=0.006],arteriovenous placement[OR=1.46,95% CI=(1.23,1.72),P<0.000 1],placement of urinary catheter[OR=1.71,95% CI=(1.25,2.36),P<0.000 01],gastrointestinal tube placement[OR=0.10,95% CI=(0.03,0.18),P=0.008],antimicrobial drug type≥3[OR=4.27,95% CI=(2.06,8.85),P<0.000 01],use of carbapenem antibiotics[OR=4.09,95% CI=(300,5.58),P<0.000 01],the use of the third-generation cephalosporin[OR=1.63,95% CI=(1.15,2.33),P=0.007],the use of quinolone antibacterials[OR=1.86,95% CI=(1.42,2.44),P<0.000 01],the use of aminoglycoside antibiotics[OR=1.99,95% CI=(1.49,2.67),P<0.000 01],use of piperacillin-tazobactam[OR=2.94,95% CI=(1.56,5.54),P=0.000 9],use of glycopeptide antibiotics[OR=3.78,95% CI=(2.48,5.78),P<0.000 01],use of sedatives[OR=3.25,95% CI=(2.06,5.14),P<0.000 01],and use of acid suppressants[OR=1.51,95% CI=(1.06,2.16),P=0.02]are risk factors for MDRO infection in ICU patients.Conclusion MDRO infections in ICU patients are associated with gender,duration of ICU stay,chronic lung disease,total length of stay,hypertension,abnormal renal function,hypoproteinemia,mechanical ventilation,duration of mechanical ventilation,arteriovenous placement,placement of urinary catheters,gastrointestinal placement,type of antimicrobial drugs≥3,use of carbapenem antibiotics,use of third-generation cephalosporin,use of quinolone antibacterials,use of aminoglycoside antibiotics,use of piperacillin-tazobactam,use of glycopeptide antibiotics,use of sedatives,use of acid suppressants,and other factors.Targeted controls of different factors such as underlying diseases,comorbidities,invasive procedures performed,and the use of antimicrobial medications and other therapeutic pharmaceuticals could limit the risk of infection in MDRO in ICU patients.

ObjectiveTo investigate the short-term efficacy of orthopedic elastic bandages on gait symmetry and walking ability in children with spastic hemiplegic cerebral palsy. MethodsFrom June, 2020 to June, 2023, 31 children with spastic hemiplegic cerebral palsy from Beijing Bo'ai Hospital were randomly divided into control group (n = 15) and experimental group (n = 16). Both groups received routine rehabilitation, while the control group received routine walking training, and the experimental group wore an orthopedic elastic bandage for walking training, for four weeks. The indexes of gait symmetry of foot deviation angle ratio (affected/healthy), step length ratio (affected/healthy), gait line ratio (affected/healthy) and standing stage ratio (affected percentage/healthy percentage) were calculated before and after training, and they were measured step width and the optional and maximum walking speed of 10-meter walk test (10MWT). ResultsOne case dropped off in the experimental group. After training, the foot deviation ratio, step length ratio, gait line ratio, and standing stage ratio improved in both groups (|t| > 2.434, P < 0.05), and they were better in the experimental group than in the control group (|t| > 2.230, P < 0.05); while the optional and maximum walking speed of 10MWT improved in both groups (|t| > 9.186, P < 0.001), and they were better in the experimental group than in the control group (|t| > 2.278, P < 0.05). ConclusionWearing orthopedic elastic bandages during rehabilitation can promote the gait symmetry and walking ability of children with spastic hemiplegic cerebral palsy.

Objective:To investigate the effect of tidal volume (Vt DI) on pulse pressure variation (ΔPP DI) during deep inspiration maneuvers in spontaneously breathing patients with sepsis and to test if adjusting ΔPP DI by Vt DI can further improve its ability in predicting fluid responsiveness (FR). Methods:Spontaneously breathing, nonintubated sepsis or septic shock patients who were admitted to the Intensive Care Unit of the Characteristic Medical Center of Chinese People's Armed Police Force and Nanjing Gaochun People's Hospital were prospectively enrolled from October 2017 to October 2019. Volume expansion (VE) was performed by infusing 500 mL saline over 20 min. Prior to VE, measurements including pulse pressure variation and tidal volume were obtained during quiet spontaneous breathing (ΔPP TB and Vt TB, respectively) and during the deep inspiration maneuver (ΔPP DI and Vt DI, respectively). Patients were classified as responders if stroke volume (SV) increased ≥ 15% after VE, otherwise non-responders. Multiple linear regression analysis was conducted to investigate the correlation of ΔPP DI with Vt DI and VE-induced percentage changes in SV (ΔSV). Receiver operating characteristic (ROC) curve analysis and the gray zone approach were used to assess the ability of each index to predict FR. Changes in gray zone limits according to the cost ratio (R = cost[false positive (FP)]/cost[false negative (FN)]) were also evaluated. Results:Of the included 31 patients, 17 were responders. There was no significant difference in ΔPP TB between fluid responders and non-responders ( P>0.05), whereas ΔPP DI was significantly higher in responders than in non-responders [(19.1±7.4)% vs (11.2±4.5)%; P=0.001]. The area under the ROC curve (AUC) of ΔPP DI predicted FR was 0.832, sensitivity of 76.47% and specificity of 71.43%, which was significantly higher than ΔPP TB (AUC=0.580, sensitivity of 47.06% and specificity of 71.43%; P<0.05). Multiple linear regression analysis showed that both Vt DI and ΔSV were independently associated with ΔPP DI ( P<0.01), the AUC of ΔPP DI adjusted by Vt DI was signigicantly higher than that of ΔPP DI alone ( P=0.03). Among the ΔPP TB, ΔPP DI and ΔPP DI/Vt DI, ΔPP DI/Vt DI had the narrowest gray zone (12.7-14.5) for the normal fluid policy (R=1), which only included 19% of the patients. When applying "restrictive" fluid management (R=2), the gray zone for ΔPP DI/Vt DI was 12.8-14.5 and included only 2 patients (6.5%). Conclusions:In spontaneously breathing, nonintubated patients with sepsis or septic shock, the ΔPP value obtained during the deep inspiration maneuver predicts FR with moderate accuracy. Given the close correlation between Vt DI and ΔPP DI, ΔPP DI adjusted by Vt DI performs better than ΔPP DI alone in predicting FR.

Objective To explore the relationship between pathogen and disease characteristics of community-acquired bacterial bloodstream sepsis in PICU.Methods The clinical data of children diagnosed as sepsis admitted to the PICU of Shengjing Hospital of China Medical University between June 2011 and June 2016 were retrospectively analyzed.Medical records were screened to confirm the diagnosis of commu-nity-acquired bacteria bloodstream sepsis.Results One hundred and ninety-one children(108 males and 83 females) had confirmed community-acquired bacteria bloodstream sepsis with the following characteristics:167 patients(87.4%) with the age less than 36 months,50 patients(26.2%) with co-existing disease,40 pa-tients(20.9%) with shock,of which 33 patients had septic shock,and 41 patients(21.5%) died.Gram-posi-tive bacteria was the predominant pathogen(73.3%,140/191).Streptococcus pneumoniae was the primary pathogen(19.9%,38/140). Conclusion Community-acquired bacteria bloodstream sepsis in PICU most commonly affects children less than 36 months of age.Gram-positive bacteria are the predominant pathogenic bacteria,the most common pathogens are Streptococcus pneumoniae,Staphylococcus epidermidis,Staphylo-coccus aureus,Streptococcus pyogenes and Escherichia coli.The highest mortality rate in septic children is caused by Pseudomonas aeruginosa.Children with co-existing disease,sepsis complicated with shock and pa-tients requiring mechanical ventilation are risk factors for death.