The poly(ADP-ribose) polymerases (PARPs) is an important group of enzymes in DNA repair pathways, especially the base excision repair (BER) for DNA single-strand breaks (SSBs) repair. Inhibition of PARP in DNA repair-defective tumors (like those with BRAC1/2 mutations) can lead to cell death and genomic instability, what is so called "synthetic lethality". Currently, PARP inhibitors combined with cytotoxic chemotherapeutic agents in the treatment of BRCA-1/2 deficient cancers are in the clinical development. In this review, we will be focused on the development of combination application of PARP inhibitors with other anticancer agents in clinical trials.

BACKGROUND:Steroid-induced osteonecrosis of the femoral head (SONFH) is a common bone disease characterized as high morbidity and poor prognosis,but the pathogenesis is unclear.Oxidative stress treatment is closely related to the occurrence and development of SONFH,and has tremendous potential in the treatment of SONFH,which can be realized by Nano-Se.OBJECTIVE:To observe the protective effect of porous Se@SiO2 nanocomposite on chondrocytes by antioxidant stress,and to further explore its mechanism of protection and treatment of SONFH.METHODS:(1) In vitro experiment:The rat chondrocytes were isolated,cultured and identified.Then,the chondrocytes were cultured with porous Se@SiO2 nanocomposite to suppress the production of reactive oxygen species (ROS).(2) In vivo experiment:A total of 36 rats were randomly divided into three groups.Steroid-induced group and experimental group were treated with intraperitoneal injection of lipopolysaccharide and intramuscular injection of methylprednisolone to induce SON FH models.Seven days after modeling,the experimental group was intraperitoneally injected with porous Se@SiO2 nanocomposite.No intervention was done in control group (blank control).At 8 weeks after modeling,rat bilateral femoral heads were taken for hematoxylin-eosin staining and Micro-CT scanning.RESULTS AND CONCLUSION:Results from the ROS detection and TUNEL apoptosis tests showed that the level of ROS in the chondrocytes was significantly reduced after intervention with Se@SiO2 (P ＜ 0.05).Micro-CT scanning findings showed that the bone mineral density,bone volume,bone area/bone volume,trabecular number,trabecular thickness,and trabecular separation in the steroid-induced and experimental groups were significantly different from those in the control group (P ＜ 0.05).Hematoxylin-eosin staining results showed smooth femoral head,normal bone cells,chondrocytes and trabecular bone,as well as few empty bone lacunae and fat cells in the control group,while in the steroid-induced group,there was bone trabecular fracture,fat cell hypertrophy fusion,a large number of empty bone lacunae and obvious osteonecrosis.These manifestations were significantly improved in the experimental group.To conclude,the porous Se@SiO2 nanocomposite has good antioxidative stress ability,suppresses the ROS production and exerts therapeutic effects on SONFH.

Objective:To evaluate the clinical efficacy of channel screw guided by O-arm navigation for the treatment of type II fragile fracture of pelvis (FFP) in the elderly.Methods:A retrospective cohort analysis was performed on clinical data of 37 patients with type II FFP admitted to Shanghai Pudong Hospital, Fudan University Pudong Medical Center from September 2019 to April 2021. There were 9 males and 28 females, aged 65-82 years [(71.8±10.1)years]. A total of 15 patients receipt channel screw fixation under O-arm navigation (surgical group) and 22 patients were treated conservatively (non-surgical group). The visual analogue scale (VAS) and Majeed functional score were compared between the two groups at emergency visit and at 1 week, 1 month, 3 months, 6 months after treatment. The accuracy of screw insertion and complications were also recorded during treatment and follow-up.Results:All patients were followed up for 6-18 months [(13.2±5.1)months]. There were no significant differences in the VAS and Majeed functional score between the two groups at emergency visit (all P>0.05). In both groups, lower VAS and higher Majeed functional score were found at 6 month after treatment as compared with those at emergency visit (all P<0.01). The VAS in surgical group was 2(1, 4)points at 1 week after treatment, lower than 4(3, 5)points in non-surgical group ( P<0.01). The VAS in surgical group was 1(1, 2)points at 1 month after treatment, lower than 3(2, 5)points in non-surgical group ( P<0.05). The Majeed functional score in surgical group was (50.2±4.2)points at 1 week after treatment, higher than (40.2±5.6)points in non-surgical group ( P<0.01). The Majeed functional score in surgical group was (73.8±5.2)points at 1 month after treatment, higher than (62.4±5.0)points in non-surgical group ( P<0.01). The two groups had no significant differences in VAS and Majeed functional score at 3 months and 6 months after treatment (all P>0.05). The accuracy of screw insertion in surgical group was 93% (14/15). In surgical group, the complication rate was 13%(2/15), including urinary tract infection in 1 patient and intraoperative screw penetration in 1, with no screw loosening or nerve and vascular injuries. In non-surgical group, the complication rate was 50%(11/22), including urinary tract infection in 5 patients, penetrating pneumonia in 5 and deep vein thrombosis in 1. The complication rate was significantly different between the two groups ( P<0.05). Conclusions:Compared with non-surgical treatment, the channel screw insertion guided by O-arm navigation can achieve precise screw placement, relieve pain early, promote functional recovery, realize accurate insertion of the screw and reduce the complication rate for type II FFP in the elderly.

Objective:To investigate the difference of HRCT imaging features between COVID-19 and the ground-glass opacity(GGO) lesion of early-stage lung carcinoma, standardize the diagnosis and treatment process of ground-glass opacity(GGO) degeneration during the epidemic.Methods:A total of 34 patients with diagnosed COVID-19 who confirmed by positive results of the new coronavirus nucleic acid test were collected as observation group 40 patients with pathologically diagnosed early-stage lung carcinoma whose preoperative HRCT examination showed pure ground glass lesions and received surgical intervention were recruited from the Department of Thoracic Surgery (The First Affiliated Hospital of Xiamen University) from January 2018 to December 2019 as the control group. The HRCT imaging features of these two groups of patients were compared and statistically analyzed.Results:The HRCT imaging features of the new type of COVID-19 showed significant difference by characteristics of multiple lesions, lesion rapid variation within 3 days, reticular pattern, vacuolar sign and clear boundary compared to the GGO lesion of early-stage lung carcinoma( P<0.05). The chinical and imaging characteristic the sex, age, with pleural effusion or not and the lesion location showed no significant difference between these 2 groups ( P>0.05). Conclusion:Contrast with inert early lung carcinoma lesions, COVID-19 disease developed rapidly. Imaging dynamic examination can provide evidences to distinguish Novel Coronavirus Pneumonia and early-stage lung carcinoma.

Objective:To investigate the clinical effect of helium-oxygen mechanical ventilation on inflammation of the diseased lung segment and diaphragm function in patients with acute respiratory distress syndrome (ARDS) caused by pneumonia who suffered difficulty weaning from mechanical ventilation.Methods:A prospective controlled study was conducted. A total of 40 patients with ARDS caused by pneumonia and requiring tracheal intubation with difficulty weaning from mechanical ventilation, admitted to the department of critical care medicine in Pingtan Branch of Fujian Medical University Union Hospital from October 2020 to December 2021 were enrolled. Patients were divided into nitrogen oxygen ventilation group and helium-oxygen ventilation group according to random number table, with 20 cases in each group. The nitrogen oxygen ventilation group was given 60% nitrogen and 40% oxygen ventilation treatment, and the helium-oxygen ventilation group was given 60% helium and 40% oxygen ventilation treatment. Peak airway pressure (Ppeak), plateau airway pressure (Pplat), tidal volume (V T), minute ventilation volume (MV) and pulse oxygen saturation (SpO 2) were collected at 0, 1, 2, 3 hours after ventilation treatment. At the same time, the concentrations of inflammatory factors interleukin-6 (IL-6) and C-reactive protein (CRP) in epithelial lining fluid in patients with diseased lung segments were measured before and after ventilation treatment for 3 hours, and the diaphragmatic excursion and the diaphragmatic thickening fraction were measured before and after ventilation treatment for 3 hours. Results:There were no significant differences in gender, age, oxygenation index, serum CRP, serum procalcitonin (PCT), body temperature, serum creatinine (SCr), alanine aminotransferase (ALT), fasting blood glucose (FPG), hemoglobin (Hb), and basic heart and lung diseases between the two groups. Under the condition that V T and SpO 2 are relatively unchanged, the airway pressure in helium-oxygen ventilation group decreased significantly after 1 hour of ventilation [Ppeak (cmH 2O, 1 cmH 2O≈0.098 kPa): 22.80±4.47 vs. 28.00±5.07, Pplat (cmH 2O): 19.15±3.90 vs. 23.20±3.81, both P < 0.05], and the airway pressure in the nitrogen oxygen ventilation group increased significantly after 1 hour [Ppeak (cmH 2O): 22.35±2.13 vs. 19.75±1.94, Pplat (cmH 2O): 18.50±1.70 vs. 16.50±1.88, both P < 0.05]. There were no significant differences in CRP and IL-6 levels in epithelial lining fluid in the diseased lung segment before and after ventilation in the nitrogen oxygen ventilation group, while the levels of these indexes in the helium-oxygen ventilation group after ventilation were significantly lower than those before ventilation, and significantly lower than those in the nitrogen oxygen ventilation group [CRP (mg/L): 10.15 (6.39, 15.84) vs. 16.10 (11.63, 18.66), IL-6 (μg/L): 1.15 (0.78, 1.86) vs. 2.67 (1.67, 4.85), both P < 0.05]. There were no statistically significant differences in the diaphragmatic excursion and the diaphragmatic thickening fraction before and after ventilation in the nitrogen oxygen ventilation group, while the above indexes in the helium-oxygen ventilation group were significantly higher than those before ventilation, and were significantly higher than those in the nitrogen oxygen ventilation group [diaphragmatic excursion (cm): 1.93 (1.69, 2.20) vs. 1.34 (1.22, 1.83), diaphragmatic thickening fraction: (48.22±8.61)% vs. (33.29±11.04)%, both P < 0.05]. Conclusion:Helium-oxygen ventilation can reduce the airway pressure of patients with mechanical ventilation, alleviate the inflammatory response of lung segment, improve the function of respiratory muscle, and is expected to be an important treatment for severe lung rehabilitation.

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052). Conclusion Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052). Conclusion Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052). Conclusion Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052). Conclusion Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.