BACKGROUND:Steroid-induced femoral head necrosis is mostly caused by long-term and extensive use of hormones,but its specific pathogenesis is not yet clear and needs further study. OBJECTIVE:To screen out the differential miRNAs in osteoclast exosomes after the intervention of Panax notoginseng saponins,and on this basis,to further construct an osteogenic-related ferroptosis regulatory network to explore the potential mechanism and research direction of steroid-induced osteonecrosis of the femoral head. METHODS:MTT assay was used to detect the toxic effects of different concentrations of dexamethasone and different mass concentrations of Panax notoginseng saponins on Raw264.7 cell line.Tartrate resistant acid phosphatase staining and TUNEL assay were used to detect the effects of Panax notoginseng saponins on osteoclast inhibition and apoptosis.Exosomes were extracted from cultured osteoclasts with Panax notoginseng saponins intervention.Exosomes from different groups were sequenced to identify differentially expressed miRNAs.CytoScape 3.9.1 was used to construct and visualize the regulatory network between differentially expressed miRNAs and mRNAs.Candidate mRNAs were screened by GO analysis and KEGG analysis.Finally,the differential genes related to ferroptosis were screened out,and the regulatory network of ferroptosis-related genes was constructed. RESULTS AND CONCLUSION:(1)The concentration of dexamethasone(0.1 μmol/L)and Panax notoginseng saponins(1 736.85 μg/mL)suitable for intervention of Raw264.7 cells was determined by MTT assay.(2)Panax notoginseng saponins had an inhibitory effect on osteoclasts and could promote their apoptosis.(3)Totally 20 differentially expressed miRNAs were identified from osteoclast-derived exosome samples,and 11 differentially expressed miRNAs related to osteogenesis were predicted by target mRNAs.The regulatory networks of 4 up-regulated differentially expressed miRNAs corresponding to 155 down-regulated candidate mRNAs and 7 down-regulated differentially expressed miRNAs corresponding to 238 up-regulated candidate mRNAs were constructed.(4)Twenty-four genes related to ferroptosis were screened out from the differential genes.Finally,12 networks were constructed(miR-98-5p/PTGS2,miR-23b-3p/PTGS2,miR-425-5p/TFRC,miR-133a-3p/TFRC,miR-185-5p/TFRC,miR-23b-3p/NFE2L2,miR-23b-3p/LAMP2,miR-98-5p/LAMP2,miR-182-5p/LAMP2,miR-182-5p/TLR4,miR-23b-3p/ZFP36,and miR-182-5p/ZFP36).These results indicate that Panax notoginseng saponins may regulate osteoblast ferroptosis by regulating the expression of miRNAs derived from osteoclast exosomes,thus providing a new idea for the study of the mechanism of steroid-induced femoral head necrosis.

Objective:To study the correlation between the acute-phase characteristics of motor evoked potential (MEP) and severities of spinal cord injury in patients with acute cervical hyperextension injury and central cord syndrome (CCS).Methods:Retrospectively analyzed were the data of 45 patients with acute cervical hyperextension injury and CCS (observation group) who had been admitted to Department of Orthopedics, Tongji Hospital Affiliated to Tongji University from December 2018 to July 2021 and 20 healthy controls. Examination of transcranial magnetic stimulation-induced MEP was performed in patients with CCS and healthy controls using a magpro x100 magnetic stimulator, and recording was conducted in bilateral abductor pollicis brevis (APB). The characteristics of MEP waveform latency, amplitude and motor threshold were described and compared between the healthy control and observation groups; the correlations were analyzed between the MEP latency and the severity of spinal cord injury [American Spinal Injury Association (ASIA) total score and motor function of Upper Extremity Motor Subscores (UEMS)] in the observation group. According to different MEP-induced states, the patients in the observation group were divided into a resting group ( n=19), a facilitation group ( n=18), and a no-waveform group ( n=8). The severity of spinal cord injury (ASIA total score) and the functional independence of the spinal cord (SCIM-Ⅲ score) were compared among the 3 groups to analyze the correlation between the MEP-induced state and the severity of spinal cord injury (ASIA total score). Results:The observation group had a significantly longer MEP latency [(30.16±6.32) ms], a significantly smaller amplitude [(0.54±0.30) mV] and a significantly higher motor threshold [(65%±11%)] than the healthy control group (all P<0.05). The MEP latency in the observation group was significantly correlated with ASIA total score ( r=-0.730, P<0.001) and UEMS ( r=-0.740, P<0.001). The ASIA total score and SCIM-Ⅲ score were significantly different among the 3 groups ( P<0.05), and the MEP-induced state was significantly correlated with the severity of spinal cord injury (ASIA total score) ( r=0.668, P<0.001). Conclusions:In patients with acute cervical hyperextension injury and CCS, the MEP latency is prolonged, the amplitude lowered, and the motor threshold enhanced. The MEP latency is strongly correlated with the severity of spinal cord injury and upper limb motor function. The MEP-induced state is also closely related to the severity of spinal cord injury.

Objective:To compare the therapeutic effects of microdissection tungsten needle and high-frequency electrosurgical generator on open thyroid surgery.Methods:95 patients who underwent open thyroid surgery from Jan. 2017 to Dec. 2017 in the Department of Breast and Thyroid Surgery, Daping Hospital of Army Military Medical University were divided into microdissection tungsten needle group ( n=50) and high-frequency electrosurgical generator group ( n=45) according to different methods. The operation time, intraoperative blood loss, postoperative drainage volume, postoperative complication rate and recurrence and metastasis rate of the two groups were compared. Results:There were no significant differences in operation time (79.3±14.7 vs 73.7±13.9, t=1.914, P=0.059) , intraoperative blood loss (31.8±9.7 vs 30.3±10.6, t=0.702, P=0.484) and postoperative drainage volume (67.3±13.0 vs 71.3±10.8, t=-1.650, P=0.102) between the two groups ( P>0.05) . There were significant differences between the two groups in temporary recurrent laryngeal nerve (RLN) injury (2% vs 17.8%,χ 2=5.518, P=0.023) and temporary hypoparathyroidism (18% vs 44%,χ 2=7.810, P=0.005) , and the results of the microdissection tungsten needle group were better than high-frequency electrosurgical generator group ( P<0.05) . There were no permanent RLN and permanent hypoparathyroidism in the two groups. There were no recurrence and metastasis during the follow-up period. Conclusions:The microdissection tungsten needle is superior to the high-frequency electrosurgical generator in the protection of RLN and parathyroid gland in open thyroid surgery, which is worthy of promotion in clinical application.

Objective:To summarize the experience of diagnosis and treatment of primary thyroid lymphoma (PTL) and improve the level of diagnosis and treatment.Methods:The clinical and pathological data of 19 patients with PTL admitted to the Department of Breast and Thyroid Surgery, Daping Hospital, Army Medical University From Mar. 2000 to Jul. 2019 were retrospectively reviewed.Results:among the 19 PTL patients, 4 were male and 15 were female, with an average age of 69 years (51-88 years) . 15 cases showed rapid enlargement of neck mass, 9 cases with swallowing obstruction, 7 cases with hoarseness and 5 cases with dyspnea. 13 cases were diagnosed by intervention, the other 6 cases were diagnosed by biopsy. There were 1 case of Hodgkin’s lymphoma and 18 cases of non Hodgkin’s lymphoma, including 13 cases of diffuse large B cell lymphoma and 4 cases of mucosa associated lymphoid tissue lymphoma. 12 cases received chemotherapy and 1 case received radiotherapy. The median follow-up period was 28 months (0-88 months) , 5 cases were lost, 6 cases died, 3 cases died of recurrence and spread of lymphoma, 3 cases died of others.Conclusions:PTL is more likely to occur in the elderly women, which is characterized by sudden enlargement of cervical mass and its related compression symptoms. The diagnosis can be confirmed by coarse needle biopsy or surgical intervention. PTL needs comprehensive treatment including surgery, chemotherapy and targeted treatment.

Objective:To evaluate the clinical value of 18F-fluorodexoyglucose (FDG) PET/CT in distinguishing benign from malignant tumors in patients with cardiac tumors. Methods:Between January 2015 and September 2018, 18F-FDG PET/CT was performed in 3 678 patents in Beijing Anzhen Hospital, and 51 of them (51/3 678, 1.39%) were diagnosed as cardiac tumors. Finally, 28 patients (10 males, 18 females; mean age (52±14) years, age range: 18-84 years) with pathological results were included. According to pathological results, patients were divided into 4 groups: group 1 with primary benign cardiac tumor ( n=9), group 2 with primary malignant cardiac tumor ( n=9), group 3 with lymphoma ( n=6) and group 4 with secondary malignant cardiac tumor ( n=4). All patients underwent early (60 min) 18F-FDG PET/CT imaging and 22 patients (6, 7, 6, 3 patients in group 1, group 2, group 3, group 4 respectively) underwent delayed (120 min) imaging. The maximum standardized uptake value (SUV max) and target/backgroud ratio (TBR) of 4 groups in early imaging and delayed imaging were calculated and compared with one-way analysis of viariace and Scheffe Post-hoc test. TBR were calcualted as SUV max/mean standardized uptake value (SUV mean) in the liver. Receiver operating characteristic (ROC) curve analysis was also performed. Results:SUV max during early imaging, defined SUV max(early), was 2.6±1.5, 9.9±4.0, 20.5±6.1, 9.2±5.8 in group 1-4 respectively ( F=21.39, P<0.01), the value of group 1 was lower than that of group 2 and 3, and the value of group 3 was the highest (all P<0.005). TBR early was 1.1±0.6, 4.1±1.6, 9.4±2.6, 3.7±2.0 in the 4 groups ( F=29.15, P<0.01), the value of group 1 was lower than that of group 2 and 3, and the value of group 3 was the highest (all P<0.005). SUV max in delayed imaging (SUV max(delay)) was 2.4±1.2, 11.0±5.9, 25.8±7.7, 13.7±7.7 respectively in the 4 groups ( F=16.01, P<0.01). TBR delay was also significantly different among the 4 groups (1.3±0.7, 5.5±2.9, 14.4±4.9, 7.9±5.0; F=14.78, P<0.01), the value of group 3 was higher than that of group 1 and 2 (all P<0.05). ROC curve analysis showed optimal cut-off values for indicating malignancy were: SUV max(early)=4.2, TBR early=1.6, SUV max(delay)=4.6, TBR delay=1.9. The corresponding sensitivities, specificities, accuracies were 19/19, 8/9, 96.4%(27/28); 19/19, 7/9, 92.9%(26/28); 16/16, 6/6, 100%(22/22); 16/16, 5/6, 95.5%(21/22), respectively. Conclusions:18F-FDG PET/CT imaging can accurately diagnose malignant cardiac tumors. Delayed imaging can further improve the accuracy for diagnosis of malignant cardiac tumors.

Purpose: Real-time detection and intervention can be used as potential measures to markedly decrease breast cancer mortality. Assessment of circulating tumor DNA (ctDNA) may offer great benefits for the management of breast cancer over time. However, the use of ctDNA to predict the effectiveness of neoadjuvant treatment and recurrence of breast cancer has rarely been studied. Methods: We prospectively recruited 31 breast cancer patients with 4 subtypes. Three time points were set in this study, including before any therapy (C1), during surgery (T), and six months after surgery (C2). We collected peripheral blood samples from all 31 patients at C1, tumor tissue from all 31 patients at T, and peripheral blood samples from 25 patients at C2. Targeted 727-gene panel sequencing was performed on ctDNA from all blood samples and tissue DNA from all tissue samples. Somatic mutations were detected and analyzed using a reference standard pipeline. Statistical analysis was performed to identify possible associations between ctDNA profiles and clinical outcomes. Results: In total, we detected 159, 271, and 70 somatic mutations in 30 C1 samples, 31 T samples, and 12 C2 samples, respectively. We identified specific genes, such as PIK3CA, TP53, and KMT2C, which were highly mutated in the tissue samples. Furthermore, mutated KMT2C observed in ctDNA of the C2 samples may be an indicator of breast cancer recurrence. Conclusion Our study highlights the potential of ctDNA analysis at different timepoints for assessing tumor progression and treatment effectiveness, as well as prediction of breast cancer recurrence.

Male breast cancer (MBC) is rare and accounts for approximately 1% of all breast cancer cases worldwide. Previous studies have suggested that several factors significantly increase the risk of MBC. Prolactinoma has the highest incidence rate among patients with functional pituitary tumors. However, whether prolactinoma is involved in the onset and progression of breast cancer remains unclear. To date, there are only five case reports globally on MBC with concurrent prolactinoma. We hereby describe the first case of MBC with prolactinoma in China. We also explored the patient's genetic profile using whole exome sequencing. Our findings may help advance our understanding of the molecular pathogenesis of MBC. Further molecular analyses of such cases are warranted to improve auxiliary molecular diagnostic methods and targeted therapy for MBC.

Objective:Recently, increasing number of lung cancer patients benefit from immune-checkpoint inhibitors (ICIs). However, the data of Chinese small cell lung cancer (SCLC) patients is limited. This study aims to analyze the response and survival data of ICIs treatment in SCLC and to explore the predictive biomarkers.Methods:Forty-seven SCLC patients who received ICIs treatment from Peking University Cancer Hospital from May 2017 to September 2019 was recruited. Clinical characteristics including sex, age, smoking status, ICIs strategy, PD-L1 expression and therapeutic efficacy were collected to explore the clinical predictive biomarkers for SCLC ICIs treatment.Results:Among the 47 patients, 18 (38.3%) cases were partial repose (PR), 11 (23.4%) were stable disease (SD), 18 (38.3%) were progressive disease (PD), and the objective response rate (ORR) was 38.3%, disease control rate (DCR) was 61.7%, the median progression-free survival (PFS) was 5.3 months. ICIs monotherapy accounts for 27.7%, the ORR was 15.4%, DCR was 53.8%, median PFS was 2.7 months. Combined therapy accounts for 72.3%, the ORR was 47.1%, DCR was 64.7%, median PFS was 5.4 months. Fourteen (29.8%) patients received ICIs as the first line treatment, their ORR was 85.7%, DCR was 100%, median PFS was 9.1 month. The ORR was not related to the age, sex, body mass index (BMI), smoking status and programmed death-ligand 1 (PD-L1) expression ( P>0.05). The ORRs were higher in patients underwent PD-L1 monotherapy ( P=0.001), combined therapy ( P=0.002) and received ICIs as the first line treatment ( P<0.001). Log-rank analysis indicated that the PFS of female patients were 12.0 months, significantly longer than 4.4 months of male patients in ICIs treatment ( P=0.038). Patients who received PD-L1 monotherapy, combined treatment, or ICIs as the first line treatment had longer PFS than their counterparts, though no statistical significant was observed ( P>0.05). Cox multivariate analysis showed that, the gender was not an independent predictor for PFS in ICIs treatment ( HR=3.777, 95% CI=0.974~30.891, P=0.054). Conclusions:Immunotherapy is an effective treatment strategy for SCLC. Patients who receive combined ICIs treatment, first line ICIs treatment and PD-L1 treatment may get greater benefits. PD-L1 expression cannot predict the response and PFS in SCLC ICIs treatment.

Objective:Recently, increasing number of lung cancer patients benefit from immune-checkpoint inhibitors (ICIs). However, the data of Chinese small cell lung cancer (SCLC) patients is limited. This study aims to analyze the response and survival data of ICIs treatment in SCLC and to explore the predictive biomarkers.Methods:Forty-seven SCLC patients who received ICIs treatment from Peking University Cancer Hospital from May 2017 to September 2019 was recruited. Clinical characteristics including sex, age, smoking status, ICIs strategy, PD-L1 expression and therapeutic efficacy were collected to explore the clinical predictive biomarkers for SCLC ICIs treatment.Results:Among the 47 patients, 18 (38.3%) cases were partial repose (PR), 11 (23.4%) were stable disease (SD), 18 (38.3%) were progressive disease (PD), and the objective response rate (ORR) was 38.3%, disease control rate (DCR) was 61.7%, the median progression-free survival (PFS) was 5.3 months. ICIs monotherapy accounts for 27.7%, the ORR was 15.4%, DCR was 53.8%, median PFS was 2.7 months. Combined therapy accounts for 72.3%, the ORR was 47.1%, DCR was 64.7%, median PFS was 5.4 months. Fourteen (29.8%) patients received ICIs as the first line treatment, their ORR was 85.7%, DCR was 100%, median PFS was 9.1 month. The ORR was not related to the age, sex, body mass index (BMI), smoking status and programmed death-ligand 1 (PD-L1) expression ( P>0.05). The ORRs were higher in patients underwent PD-L1 monotherapy ( P=0.001), combined therapy ( P=0.002) and received ICIs as the first line treatment ( P<0.001). Log-rank analysis indicated that the PFS of female patients were 12.0 months, significantly longer than 4.4 months of male patients in ICIs treatment ( P=0.038). Patients who received PD-L1 monotherapy, combined treatment, or ICIs as the first line treatment had longer PFS than their counterparts, though no statistical significant was observed ( P>0.05). Cox multivariate analysis showed that, the gender was not an independent predictor for PFS in ICIs treatment ( HR=3.777, 95% CI=0.974~30.891, P=0.054). Conclusions:Immunotherapy is an effective treatment strategy for SCLC. Patients who receive combined ICIs treatment, first line ICIs treatment and PD-L1 treatment may get greater benefits. PD-L1 expression cannot predict the response and PFS in SCLC ICIs treatment.

OBJECTIVE： To promote rational use of proton pump inhibitors （PPIs） during perioperative period. METHODS： PDCA （Plan， Do， Check， Action） cycle management was used， the irrational use of PPIs of 300 medical records in neurosurgery department of our hospital were collected. The reasons were analyzed， management target was formulated and measures were implemented. The effects of management were evaluated through comparing the rate of irrational drug use and ratio of irrational type of PPIs in 300 medical records of neurosurgery department during perioperative period after management. RESULTS： Through collecting related data to confirm risk factors of stress ulcer， establishing rationality evaluation criteria for perioperative prophylactic use of PPIs， conducting rational drug use training among medical staff， drawing up various management systems and strengthening supervision and management， the rate of irrational use of PPIs was decreased significantly in our hospital； the number of irrational drug use cases decreased from 240 before management to 156 after management， among which the rate of prophylactic drug use without indication decreased from 37.33％ to 29.00％ （P＜0.05）； the irrational dosage rate decreased from 11.33％ to 6.33％ （P＜0.05）； the rate of irrational dosing frequency dropped from 12.67％ to 5.00％ （P＜0.01）. CONCLUSIONS： PDCA cycle management of our hospital can standardize the prophylactic use of PPIs in neurosurgery department during perioperative period and promote rational use of PPIs.