Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells.

Human mononuclear phagocytes comprise phenotypically and functionally overlapping subsets of dendritic cells (DCs) and monocytes, but the extent of their heterogeneity and distinct markers for subset identification remains elusive. By integrating high-dimensional single-cell protein and RNA expression data, we identified distinct markers to delineate monocytes from conventional DC2 (cDC2s). Using CD88 and CD89 for monocytes and HLA-DQ and FcεRIα for cDC2s allowed for their specific identification in blood and tissues. We also showed that cDC2s could be subdivided into phenotypically and functionally distinct subsets based on CD5, CD163, and CD14 expression, including a distinct subset of circulating inflammatory CD5-CD163+CD14+ cells related to previously defined DC3s. These inflammatory DC3s were expanded in systemic lupus erythematosus patients and correlated with disease activity. These findings further unravel the heterogeneity of DC subpopulations in health and disease and may pave the way for the identification of specific DC subset-targeting therapies.

[Transperineal targeted prostate puncture combined with rapid pathological examination in the diagnosis of prostate cancer].

Exploring the clinical value of multiparametric magnetic resonance (Mp-MRI)-cognitive fusion method of targeted transperineal prostate puncture combined with rapid pathological diagnosis. Patients with suspected prostate cancer admitted to our hospital from 2022.01 to 2023.05 were selected as the study subjects, and Mp-MRI was performed and the suspected lesions were scored by the Prostate Imaging Reporting and Data System (PI-RADS). The enrolled patients were randomly divided into the transperineal prostate targeted puncture plus rapid pathology group (experimental group) and the transperineal prostate systematic combined targeted puncture plus conventional pathology group (control group), and the positive puncture rate, pathological findings, and complications were analyzed to compare the differences between the two groups. A total of 100 patients were enrolled, 53 in the experimental group [age 55-89 years, (73.17±7.79) years; tPSA 7.01-100 µg/L, mean 21.34 (12.38, 44.42) µg/L]and 47 in the control group [age 60-87 years, (71.96±7.07) years; tPSA 6.11-98.82 µg/L, mean 18.77 (9.04, 38.09) µg/L], and there was no significant difference between the two groups in the diagnostic positivity rate of overall PCa and clinically significant PCa (P>0.05); there was no significant difference in the highest Gleason score of pathological tissues between the two groups (P>0.05); the number of cases of medically induced sarcoid hematuria in the experimental group were significantly reduced compared with the control group (P<0.05). In terms of biopsy pain score (VAS), patients in the experimental group experienced less pain than those in the control group (P<0.05). The Mp-MRI-cognitive fusion method of transperineal targeted prostate puncture combined with rapid frozen section pathological examination can provide rapid and accurate pathological results, reduce the chance of post-puncture complications, and alleviate the pain caused by puncture sampling, which has high clinical value.

[Analysis of clinical effect of arthroscopic release at different time in treating knee adhesion after arthroscopic surgery].

Objective: To explore the efficacy of arthroscopic release in treating postoperative knee adhesion and investigate the influence of release timing on the treatment outcomes. Methods: A total of 50 patients who accepted arthroscopic release in Peking University Third Hospital from February 2017 to December 2021 were included in the retrospective cohort. The study cohort comprised 28 men and 22 women, with a mean age of (30.8±11.9) years. All the primary surgeries were manipulated under arthroscopes. A comparison was made between pre-and postoperative range of motion (ROM), visual analog scale (VAS), International Knee Documentation Committee (IKDC) scores, and Tegner activity scale scores for the patients. According to the interval between the appearance of adhesion and arthroscopic release, the patients were divided into four groups:<3 months group (n=12), 3-6 months group (n=16),>6-12 months group (n=14), and>12 months group (n=8). Inter-group comparisons on postoperative ROM, IKDC scores, and Tegner activity scale scores and improvement values of each outcome were conducted. Results: All the patients were followed up for (36.4±19.7) months. Patients gained significant improvement in flexion, extension, IKDC scores, and Tegner scores (125.0°±20.0° vs 75.7°±27.5°, 2.3°±4.8° vs 7.4°±7.3°, 69.8±17.7 vs 51.4±12.8, 4.1±2.1 vs 2.2±1.1) (all P<0.05), while the VAS scores did not show significant improvement. There were no significant differences among different groups in postoperative extension, IKDC scores or Tegner scores, nor in their improvements. However, patients in the ≤6 months group could gain better postoperative flexion and improvement in flexion than those in the >6 months group (129.9°±20.0° vs 118.8°±17.4°, 58.6°±32.8° vs 37.3°±23.1°) (P<0.05). Conclusions: Arthroscopic release presents a great effect in treating knee adhesion after arthroscopic operation. Once the symptoms of adhesion appear and physical rehabilitation fails to improve the ROM, one should accept early surgical intervention (less than 6 months) for a better outcome.

[Clinical analysis of adverse reactions in patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis treated with delamanid-containing regimen].

Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.

[Diagnosis and treatment of 21-hydroxylase deficiency with testicular adrenal rest tumors:a report of three cases and literature review].

Objective: To provide insight into the diagnosis for clinicians, the clinical characteristics, diagnosis and treatment history of 3 patients with 21-hydroxylase deficiency (21-OHD) and testicular adrenal rest tumors (TART) were analyzed. Methods: The clinical, laboratory and imaging data of 3 male patients with 21-OHD and TART, confirmed with CYP21 gene sequencing, from May 2010 to May 2021 in the First Medical Center of Chinese PLA General Hospital were analyzed retrospectively. The treatment strategy and clinical outcome were followed up. Results: All the 3 patients were first diagnosed with bilateral adrenal mass at the age of 27-42 years old. They were 145-162 cm tall. The levels of progesterone, 17-hydroxyprogesterone, and adrenocorticotropic hormone (ACTH) of the 3 patients were relatively high, and that of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) of the 3 patients were low. Testosterone level of 1 patient was significantly elevated, and that of the other 2 patients was below the lower limit of normal range. Testicular ultrasound showed heterogeneous hyperechoic masses in both testes. CT of the adrenal glands showed bilateral adrenal enlargement with mass. All 3 patients were treated with dexamethasone. After 4-96 months of follow-up, 17-hydroxyprogesterone level was kept above the median normal level. One of the patients got married and had a baby after treatment. The sizes of adrenal hyperplasia and testicular masses reduced to various degrees with the change of the testicular masses being proportional to that of adrenal hyperplasia. Conclusions: Patients with 21-OHD are prone to have TART, leading to the impaired testicular function. Early glucocorticold therapy is beneficial to the reduction of TART and restoration of testicular function.

[Mid-to-long term clinical outcomes and predictors after anterior cruciate ligament revision].

OBJECTIVE: To assess the mid-to-long term clinical outcomes after anterior cruciate ligament (ACL) revision surgery and to analyze their predictors. METHODS: The medical records of 235 patients undergoing ACL revision surgery between Jan. 2001 and Dec. 2015 at Department of Sports Medicine, Peking University Third Hospital were reviewed. Data were collected including demographic information, information related to revision surgery (time and cause of graft failure, date of revision surgery, surgical technique, combined injuries and management, etc.), as well as information related to primary ACL reconstruction (time, cause and mechanism of first-time ACL rupture, date of primary ACL reconstruction, surgical technique, combined injuries and management, etc.). Patients were followed up at least 2 years after revision surgery for clinical outcomes [Tegner score, Lysholm score, and International Knee Documentation Committee (IKDC) subjective knee score]. Post-revision surgeries on the involved knee and the contralateral knee joint were also documented. Multivariate regression model was used to analyze the predictors of clinical outcomes after ACL revision surgery. RESULTS: A total of 166 (70.63%) patients were followed up at a mean of (4.44±2.40) years (2.03-14.63 years). Clinical outcomes improved significantly at the last follow-up from pre-operative level, with the Lysholm, Tegner, and IKDC scores improving from 70.51±21.25, 3.39±1.77, 63.78±15.04 to 88.64±14.36, 4.67±1.739, 80.23±13.31 (P < 0.05), respectively. Three (1.81%) patients experienced infection while 39 (23.49%) patients underwent surgery after revision surgery during the follow-up. Compared with that those occurred during sports, graft failure that occurred during daily activities or due to surgical technical errors that led to poorer clinical outcomes, with the Lysholm, Tegner, and IKDC scores of 9.90 (95%CI: 1.49-18.31), 1.41 (95%CI: 0.10-2.72), 10.35 (95%CI: 0.17-20.54), and 8.53 (95%CI: 1.31-15.75), 1.28 (95%CI: 0.14-2.43), 9.39 (95%CI: 1.03-17.74) lower, respectively. Compared with antero-medial portal, transtibial technique for placement of the femoral bone tunnel showed poorer Lysholm scores of 11.18 (95%CI: 4.73-17.63, P=0.001). Concurrent repair of medial meniscus yielded higher IKDC scores of 11.06 (95%CI: 1.21-20.92, P=0.029) than those with intact medical meniscus. Other factors showed no significant effect. CONCLUSION: ACL revision surgery is able to restore knee stability and improve knee function. Graft failure caused by sports, concurrent repair of medical meniscus and antero-medial portal technique predicts better outcomes after revision surgery.

[Utility of the type 3 portable monitor for the diagnosis of sleep disordered breathing in patients with stable heart failure].

Objective: To evaluate the utility of a type 3 portable monitor (PM) at home for the diagnosis of sleep disordered breathing (SDB) in patients with stable congestive heart failure (CHF). Methods: Seventy-six consecutive patients with CHF (61 males, 15 females, mean±standard deviation age (57.0±16.9) years) were enrolled from the sleep center of Peking university People's Hospital during January 2016 to January 2019, and underwent overnight, unattended home sleep apnea testing (HSAT) with a portable monitor followed by an overnight simultaneous polysomnogram (PSG) with in-laboratory portable monitor (in-lab PM) recording within one week. The consistency of apnea hypopnea index (AHI), obstructive sleep apnea index (OAI), central sleep apnea index (CAI) between HSAT and PSG as well as the in-lab PM and PSG were analyzed by Bland-Altman plot; the sensitivity and specificity of PM for the diagnosis of SDB in patients with CHF were evaluated. Results: The number of patients included in the final analysis were 65 in HSAT, 63 in in-lab PM and 65 in PSG. AHI [M(Q1,Q3)] was 26.1 (10.9,40.1) events/h by HSAT, 27.9 (11.3,43.2) events/h by in-lab PM, both were not different from AHI 29.0 (10.2,45.0) events/h by PSG (P>0.05). The AHI, OAI and CAI assessed by HSAT correlated significantly with those by PSG (r=0.892, 0.903, 0.831, P<0.05). Bland-Altman analysis of AHI, OAI, CAI by PSG versus HSAT showed a mean difference of 3.1 events/h, 0.8 events/h, 1.2 events/h; limits of consistency were -15.2 to 21.4 events/h, -9.7 to 11.3 events/h, -10.9 to 13.2 events/h, respectively. Based on a threshold of AHI ≥5 events/h, HSAT had 94.6% sensitivity, 75% specificity, compared to PSG. For detecting Cheyne-Stokes respiration (CSR), a sensitivity of 96.4%,a specificity of 97.2% were achieved, compared to PSG. Conclusion: Type 3 PM can be used to diagnose SDB in patients with CHF.

[Emergency training need and effect evaluation analysis of novel coronavirus pneumonia in centers of disease control and prevention].

A questionnaire was used to investigate the emergency training needs of novel coronavirus pneumonia of disease prevention and control institutions in provinces, deputy provincial level regions and cities specifically designated in the state plan, and the effect evaluation of emergency training activities conducted by Chinese Center for Disease Control and Prevention (China CDC). The results showed that 67.4% of 47 disease prevention and control institutions (31/46) believed that the emergency training at the initial stage of the epidemic should be conducted as soon as possible, and the form of network training should be given priority. The training should focus on the urgently needed technologies such as epidemiological investigation, formulation and response of prevention and control strategies, laboratory testing, etc. The teaching materials should highlight pertinence and practicability and be presented in the form of electronic video. The average satisfaction score of the video training conducted by China CDC was (8.81±1.125) and the score of audio-video courseware was (8.97±0.893). The needs analysis and evaluation of novel coronavirus pneumonia prevention and control in disease prevention and control institutions could provide reference for the follow-up training and improve the emergency training management.

[Efficacy and safety of Montgomery T-tube placement for benign complex subglottic tracheal stenosis: a retrospective analysis of 29 cases].

Objective: To analyze the efficacy and safety of Montgomery T-tube (T-tube) placement for benign complex subglottic tracheal stenosis. Methods: A retrospective analysis of the clinical data of 29 patients with benign complex subglottic tracheal stenosis receiving T-tube placement in Beijing Tiantan Hospital from May 2015 to December 2019. The causes were postintubation tracheal stenosis [27 cases (93.1%), including 21 cases (72.4%) of tracheal stenosis after tracheotomy, 6 cases (20.7%) of tracheal stenosis after tracheal intubation], cervical post-traumatic tracheal stenosis (1 case, 3.4%) and tuberculous tracheal stenosis (1 case, 3.4%), respectively. Three-dimensional reconstruction of tracheal computerized tomography (CT) and bronchoscopy were used to grade the stenosis according to Cotton-Myer classification system before bronchoscopic intervention. The degree of stenosis was Cotton-Myer grade Ⅱ (7 cases, 24.1%), grade Ⅲ (11 cases, 37.9%) and grade Ⅳ (11 cases, 37.9%), respectively. All cases received placement of T-tubes and follow-up. Fisher's exact test was used for comparison between groups. Results: T-tube placement was performed 39 times in 29 patients. T-tubes were successfully placed for 24 cases (82.8%). The main complication during the operation was tracheal mucosal tear (6 cases, 20.7%), which resolved in all cases within 2 weeks. The main postoperative complication was secretion retention (27 cases, 93.1%), which was relieved after home nebulization treatment in 26 cases; and followed by granulation hyperplasia, especially located in T-tube upper margin (12 cases, 41.4%), of which 8 cases were cured after bronchoscopic intervention. None of the patients had T-tube migration. There were no statistically significant differences in the success rate of T-tube placement and the incidence of major complications in patients with benign complex subglottic tracheal stenosis with different degrees of stenosis. After 18 months to 24 months of follow-up, attempt was made to remove the T-tube in 9 patients but failed in 4 patients. The failure was due to collapse of the airway after the T-tube was removed. Conclusion: T-tube placement is a safe and reliable treatment for benign complex subglottic tracheal stenosis with high efficiency and manageable complications.

[Efficacy of endovascular treatment of distal aortic dissection involving abdominal visceral segment with bare-metal stents related technique].

Objective: To investigate the effect of bare-metal stent related technique on distal aortic dissection involving abdominal visceral segment. Methods: A retrospective analysis was performed on clinical data of 33 patients with distal aortic dissection involved abdominal visceral segment, who hospitalized in the Vascular Surgery Department of Shanghai Changhai Hospital from July 2012 to September 2019. The effect of the treatment was evaluated according to the clinical and preoperative, intraoperative and follow-up imaging data derived from (aorta computed tomography angiography (CTA) and digital subtraction angiography (DSA)) as well as the changes of the maximal diameter of the aorta and the thrombosis of the false lumen of the dissection. The criteria were as follows: the maximum diameter change of aortic dissection<5 mm was defined as stable; the maximum diameter decrease of aortic dissection≥5 mm was defined as effective reduction; the maximum diameter increase of aortic dissection≥5 mm was defined as expansion; the definition of diameter change of false lumen was the same as above. The hospital complications, clinical symptoms and survival were recorded. Results: There were 28 male patients in this cohort, the mean age was (57.6±4.9) years old. Twenty-one patients were treated with bare-metal stent and coils technique, of which 8 patients were jointly treated with stent grafts. Twelve patients were treated with multi-layer bare-metal stent technique, of which 4 patients were jointly treated with stent grafts. Intraoperative DSA image results showed that the visceral arteries were patent during the treatment, and the blood flow velocity of the false lumen was reduced in all 33 patients. There were no adverse events such as distal outflow tract embolism and coil displacement during the operation. During the period of hospitalization, one patient developed intimal rupture of subrenal abdominal aortic dissection on the fourth day after operation and emergency endovascular graft exclusion was performed for abdominal aortic dissection, and the patient recovered well from the emergency operation. The follow-up time was (16.7±14.0) months. One patient died 1 year after surgery due to non-disease-related factors. Follow-up CTA imaging results showed that the maximum diameter of the aorta in abdominal visceral segment tended to be smaller ((39.1±13.4) mm vs. (41.3±11.9) mm, P=0.469), and the maximum diameter of the false lumen was significantly reduced ((16.2±12.9) mm vs. (23.5±10.7) mm, P=0.014). The maximum diameter of the aortic dissection was reduced in 12 cases, stable in 19 cases, expanded in 2 cases. The maximum diameter of the false lumen was effectively reduced in 22 cases, stable in 10 cases, and expanded in 1 case. Four patients developed small endoleak in the false lumen, one of them was nearby the renal artery stent, and the remaining patients experienced complete thrombosis of the false lumen. Conclusions: Endovascular treatment of distal aortic dissection involving abdominal visceral segment with bare-metal stents related technique could promote the shrink and the thrombosis of the false lumen, and slow down the blood flow from the tear into the false lumen in the setting of patency of visceral arteries.

[Key data elements for clinical management and outcomes of patients with coronary artery disease: definitions from Coronary Artery Disease and Creative Antithrombotic Clinical Research Collaboration (CardiaCare)].

Objective: To develop a set of data elements and standardized definitions of Coronary Artery Disease and Creative Antithrombotic Clinical Research Collaboration (CardiaCare), aiming to facilitate the exchange of disparate data sources, enhance the abilities to support multicenter researches, and subsequently ensure the databases use under standardized process and criteria. Methods: The Cardiacare writing committee members reviewed data elements and definitions from published guidelines, clinical trials, databases, and standardized documents, then determined the data elements and standardized definitions, which should be included in CardiaCare. The writing committee also considered the specific domestic clinical management strategies during the establishment of Cardiacare. The resulting documents provide a series of key data elements and standardized definitions used in the management of coronary artery disease patients. Key data elements from CardiaCare could be sorted by clinical management flowsheet and outcome from hospitalization to long-term follow-up. Results: The Cardiacare standardized set comprised 864 data elements from admission to post-hospital follow-up visit. There were 8 tables in the documents, including demographic and admission information (23 elements), medical history and risk factors (102 elements), clinical presentations and diagnosis (22 elements), diagnostic and laboratory tests (111 elements), interventional diagnosis and treatment (118 elements), pharmacological therapy (213 elements), clinical outcomes (161 elements), and special subpopulations (114 elements: 87 elements for transcatheter valve replacement and 27 elements with cardiac rehabilitation). Conclusions: The Cardiacare standardized data elements set could provide support for real-world clinical research in consecutive data collection and databases mining. A wider applicability in various settings of CardiaCare needs to be explored further.

Combination therapy with the CDK7 inhibitor and the tyrosine kinase inhibitor exerts synergistic anticancer effects against MYCN-amplified neuroblastoma.

Patients with neuroblastoma due to MYCN oncogene amplification and consequent N-Myc oncoprotein overexpression have very poor prognosis. The cyclin-dependent kinase 7 (CDK7)/super-enhancer inhibitor THZ1 suppresses MYCN gene transcription, reduces neuroblastoma cell proliferation, but does not cause significant cell death. The protein kinase phosphatase 1 nuclear targeting subunit (PNUTS) has recently been shown to interact with c-Myc protein and suppresses c-Myc protein degradation. Here we screened the U.S. Food and Drug Administration-Approved Oncology Drugs Set V from the National Cancer Institute, and identified tyrosine kinase inhibitors (TKIs), including ponatinib and lapatinib, as the Approved Oncology Drugs exerting the best synergistic anticancer effects with THZ1 in MYCN-amplified neuroblastoma cells. Combination therapy with THZ1 and ponatinib or lapatinib synergistically induced neuroblastoma cell apoptosis, while having little effects in normal nonmalignant cells. Differential gene expression analysis identified PNUTS as one of the genes most synergistically reduced by the combination therapy. Reverse transcription polymerase chain reaction and immunoblot analyses confirmed that THZ1 and the TKIs synergistically downregulated PNUTS mRNA and protein expression and reduced N-Myc protein but not N-Myc mRNA expression. In addition, PNUTS knockdown resulted in decreased N-Myc protein but not mRNA expression and decreased MYCN-amplified neuroblastoma cell proliferation and survival. As CDK7 inhibitors are currently under clinical evaluation in patients, our data suggest the addition of the TKI ponatinib or lapatinib in CDK7 inhibitor clinical trials in patients.

Melatonin activates autophagy via the NF-κB signaling pathway to prevent extracellular matrix degeneration in intervertebral disc.

OBJECTIVE: This study investigated whether melatonin alleviates intervertebral disc degeneration (IVDD) by promoting autophagy through inhibiting the NF-κB signaling pathway. METHODS: Magnetic resonance imaging (MRI), hematoxylin and eosin (H&E) staining and Safranin-O staining were used to measure disc degeneration in rat needle puncture IVDD models, and melatonin was injected intraperitoneally in the treated group to test its function. The expression of autophagy and extracellular matrix (ECM) degeneration related-markers were measured in the discs using immunohistochemistry. Transmission electron microscopy was used to evaluate the activation of autophagy in human nucleus pulposus (NP) tissues with different degenerated statuses. The expression of autophagy and disc degeneration related-markers were detected in NP cells by Western blot, RT-qPCR, and immunofluorescence analyses. NF-κB signaling pathway involvement was studied by lentivirus-mediated knockdown, Western blotting, and immunohistochemistry and immunofluorescence staining. RESULTS: Melatonin prevented IVDD development in vivo and in vitro. Compared to non-degenerated disc tissues, degenerated human NP tissues showed a decrease in the autophagy-specific marker LC3B and the numbers of autophagosomes and autolysosomes, whereas the p62 level was increased; similar results were observed in rat IVDD models, indicating a negative correlation between autophagy and IVDD. Furthermore, both in vivo and in vitro studies found that melatonin application induced autophagy and reduced ECM disc degradation. Melatonin was also shown to regulate autophagy by inhibiting the NF-κB signaling pathway in vivo and vitro. CONCLUSION: This study indicates that melatonin prevents IVDD by promoting autophagy, indicating its possible therapeutic potential for controlling the progression of IVDD.

Pleiotropic loci underlying bone mineral density and bone size identified by a bivariate genome-wide association analysis.

Aiming to identify pleiotropic genomic loci for bone mineral density and bone size, we performed a bivariate GWAS in five discovery samples and replicated in two large-scale samples. We identified 2 novel loci at 2q37.1 and 6q26. Our findings provide insight into common genetic architecture underlying both traits. INTRODUCTION: Bone mineral density (BMD) and bone size (BS) are two important factors that contribute to the development of osteoporosis and osteoporotic fracture. Both BMD and BS are highly heritable and they are genetically correlated. In this study, we aim to identify pleiotropic loci associated with BMD and BS. METHODS: We conducted a bivariate genome-wide association (GWA) analysis of hip BMD and hip BS in 6180 participants from 5 samples, followed by in silico replication in the UK Biobank study of BMD (N = 426,824) and the deCODE study of BS (N = 28,954), respectively. RESULTS: SNPs from 2 genomic loci were significant at the genome-wide significance (GWS) level (p lt; 5 × 10-8) in the discovery samples and were successfully replicated in the replication samples (2q37.1, lead SNP rs7575512, discovery p = 1.49 × 10-10, replication p = 0.05; 6q26, lead SNP rs1040724, discovery p = 1.95 × 10-8, replication p = 0.03). Functional annotations suggested functional relevance of the identified variants to bone development. CONCLUSION: Our findings provide insight into the common genetic architecture underlying BMD and BS, and enhance our understanding of the potential mechanism of osteoporosis fracture.

[Clinical aspects of pregnancy-related lymphocytic hypophysitis].

Objective: To analyze clinical features, diagnosis, treatment and prognosis of pregnancy-related lymphocytic hypophysitis (LyH). Methods: The clinical data of 16 cases diagnosed as pregnancy-related LyH at Chinese PLA General Hospital between October 2010 and November 2019 were reviewed. Results: Sixteen patients were included (aged 20-40 years). All patients' symptoms occurred from the last 2 months of pregnancy to 12 months postpartum, with 6 cases in the third trimester and 10 cases during postpartum, and all the patients were diagnosed after delivery. Six patients had lymphocytic adenohypophysitis (LAH), 4 patients had lymphocytic infundibuloneurohypophysitis (LINH), 4 patients had lymphocytic panhypophysitis (LPH), and 2 had lymphocytic hypothalamitis. Eight patients presented with symptoms of intracranial space-occupying lesions, 14 patients had symptoms of anteriorpituitary hormone deficiencies, 9 patients had central diabetes insipidus (CDI), and 2 had hyperprolactinemia. Pituitary MRI showed that the pituitary presented with diffuse enlargement, pituitary stalk thickening, disappearing of high-intensity signals in posterior pituitary and space-occupying lesions in the infundibulum of hypothalamus. Nine patients were treated with immunosuppressive agent, 3 patients alleviated the space-occupying effects after surgery, and 4 patients recovered spontaneously. Fourteen patients were followed up with a period of 3-98 months. Four patients had a relapse, 2 patients had a complete remission, and 12 patients needed long-term hormone replacement therapy. Conclusions: Clinical manifestations of pregnancy-related LyH are diverse. LyH should be suspected in pregnant or postpartum women with a sellar mass to avoid missed diagnosis or misdiagnosis. Immunosuppressant therapy is effective. Overall, LyH patients have a favorable prognosis.

[Efficacy and influencing factors of interventional bronchoscopy for the treatment of scarring airway stenosis: a multicenter retrospective investigation from China].

Objectives: To evaluate the efficacy of interventional bronchoscopy for the treatment of scarring airway stenosis and to analyze the influencing factors related to the success rate. Methods: Between January 2013 to December 2016, 301 patients with scarring airway stenosis treated by interventional bronchoscopy in 18 tertiary hospitals were reviewed retrospectively. The methods of interventional bronchoscopy included electric knife cutting, laser cauterization, balloon dilation, cryotherapy, local drug usage and/or stenting. Airway stenosis characteristics and patients' performance status at baseline and after interventional bronchoscopy were recorded. The interval days between the first two interventional bronchoscopy treatment (maintained patency time) and the final treatment efficacy were recorded. Results: The clinical stability rate of interventional bronchoscopy for the treatment of scarring tracheal stenosis was 67.8% (204/301) . Stenosis sites (OR 1.548; 95% CI: 1.038-2.307, P=0.032) , dyspnea index (OR 2.140; 95% CI: 1.604-2.855, P<0.001) , and interventional method (OR 0.458; 95% CI: 0.267-0.787, P=0.005) were independent predictors associated with the efficacy of interventional bronchoscopy treatment. Stenosis sites (OR 1.508; 95% CI: 1.273-1.787, P<0.001) , stenosis grade (OR 1.581; 95% CI: 1.029-2.067, P=0.001) , anesthesia method (OR 1.581; 95% CI: 1.029-2.067, P<0.001) , and local drug usage (OR 1.304; 95% CI: 1.135-1.497, P<0.001) were independent predictors associated with the maintained patency time after first interventional bronchoscopy treatment. Conclusion: Interventional bronchoscopy is a useful treatment method for scarring airway stenosis. Enough attention should be paid to influencing factors in order to improve treatment efficacy during the treatment process.

[Clinical efficacy and safety of apatinib combined with chemotherapy for osteosarcoma and soft tissue sarcoma with pulmonary metastasis].

Objective: To compare the clinical efficacy and drug safety between oral apatinib combined with conventional chemotherapy and conventional chemotherapy alone for the treatment of osteosarcoma and soft tissue sarcoma patients with pulmonary metastasis. Methods: Thirty-three osteosarcoma and soft tissue sarcoma patients with pulmonary metastasis who were treated in the Department of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of China Medical University from January 2015 to December 2017 were enrolled in this study. Patients with osteosarcoma received methotrexate, adriamycin (ADM), cisplatin (CDDP), ifosfamide (IFO) sequential regimen; patients with soft tissue sarcoma were treated with IFO and ADM regimen. Eighteen of these patients received an additional oral dose of apatinib. The patients were followed up regularly for changes in primary tumors and metastases, adverse reactions and prognosis. Results: Before treatment, the maximum diameter of pulmonary metastases in patients of apatinib group and routine treatment group were (4.46±1.70) cm and (4.53±2.00) cm, respectively, without significant difference (P=0.909). After treatment, the maximum diameter of pulmonary metastases in patients of apatinib group was (1.46±1.39) cm, significantly smaller than (3.02±1.20) cm of routine treatment group (P=0.002). After treatment, the maximum diameter of the primary lesions in the apatinib group and the conventional treatment group median decreased 0.31 cm and 0.12 cm, respectively, without significant difference (P=0.542). After treatment, the maximum diameter of the lung metastases in the apatinib group median decreased 0.59 cm, significantly more than 0.18 cm of the conventional treatment group (P=0.027). The median progression-free survival (PFS) was 9.4 months in the 33 patients. The median PFS was 9.6 months and 8.3 months in the apatinib group and the conventional treatment group, respectively, without significant difference (P=0.593). Specific adverse reactions both occurred in apatinib group and routine treatment group, mainly including oral mucosal reactions and digestive tract reactions (including nausea, vomiting and diarrhea). Conclusions: Apatinib can effectively reduce the volume of primary and metastatic lesions in patients with bone and soft tissue sarcoma accompanied by lung metastasis without reducing the survival rate or causing uncontrollable adverse reactions. The safety and clinical efficacy of apatinib are significant.

[Differences of brain functional alterations between subtypes of Cushing's syndrome patients].

Objective: To compare the differences of brain functional damage of subtypes of patients with Cushing's syndrome (CS). Methods: A total of 11 adrenocorticotropic hormone (ACTH)-dependent CS patients and 29 ACTH-independent CS patients were recruited from Chinese PLA General Hospital between September 2015 and March 2017 with confirmed CS. The psychiatric scales and brain task functional magnetic resonance imaging (fMRI) were evaluated. Results: A total of 40 patients (34 females, 6 males) with a mean age of (39.20±12.10) years and a median education level of 12 (9, 16) years were enrolled. ACTH-dependent patients had significantly worse performance than the ACTH-independent patients in response to the depression evaluation (64.6±6.1 vs 56.2±12.8, P=0.008), positive emotion (17.8±4.2 vs 24.3±7.2, P=0.008) and CS life quality [31(29,33) vs 42(29,51), P=0.040]. In the reaction to positive target pictures, ACTH-dependent CS patients showed stronger activation in left superior temporal gyrus compared with patients in ACTH-independent group, while the activation degree of their bilateral dorsal anterior cingulate cortex, bilateralsuperior frontal gyrus and left middle frontal gyrus was much worse. In the reactions to negative target pictures, ACTH-dependent CS patients had weaker activation in bilateral cerebellum, left superior frontal gyrus, left middle frontal gyrus, left precuneus and right postcentral gyrus, compared with patients in the ACTH-independent CS group (P<0.01, AlphaSim corrected). The activation degree of some regions whose brain function was different between the two groups was correlated to the cortisol level, ACTH level, 24 h urinary free cortisol (UFC) level, depression evaluation and negative emotion assessment (all P<0.05). Conclusions: The severity of the depression and the life quality of patients in ACTH-dependent group are worse than ACTH-independent CS patients. The brain function of ACTH-dependent CS patients is much weaker.

[A preliminary study of different methods of anesthesia for painless bronchoscopy].

Objective: This study aimed to explore a feasible method of anesthesia for painless bronchoscopy. Methods: A total of 120 patients receiving flexible bronchoscopy in Beijing Tiantan Hospital during the period from February, 8, 2018 to May, 4, 2018, were randomly divided into 3 groups, including group A (using lidocaine for local anesthesia), group B (using lidocaine + midazolam + fentanyl), and group C (using lidocaine + propofol + sufentanil). There were 41 patients in group A, 38 in group B and 41 in group C. The changes in systolic blood pressure, diastolic blood pressure, heart rate and pulse oxygen saturation(SpO(2)) in each group were recorded in different points of time. The safety of different methods of anesthesia was observed by recording vital signs and adverse events. Moreover, the visual analogue scale (VAS) was used to observe the patient's tolerance and satisfaction of the operation. Results: The intraoperative systolic blood pressure and diastolic blood pressure in group C were significantly lower than those in group A and B (P<0.05). Six cases in group C had hypotension, 3 of whom required vasoactive drugs. The differences of SpO(2) between the 3 groups showed no statistical significance (P>0.05), while patients in group C were prone to decrease in SpO(2). Eighteen patients in group C had hypoxemia during operation. But after treated with improving ventilation, the SpO(2) of those patients could be restored to normal. Compared with those in group C, patients in group A and group B showed significant discomfort, cough, and more pharyngeal pain (P<0.05). However, there were no significant differences in the degree of cough and pain between group A and group B (P>0.05). Most patients in group C had no uncomfortable sensation during the operation (P<0.05), and the willingness to re-examination was significantly higher than that in group A and group B (P<0.05). Conclusion: Propofol combined with sufentanil could achieve better painless effect, improve patient comfort and tolerance, and reduce intraoperative memory, but was prone to causing hypoxemia and hypotension. The decline of intraoperative SpO(2) could be corrected by establishing artificial airway, while the decrease of blood pressure could be corrected by applying vasoactive drugs, which were relatively safe.

Transcatheter aortic valve replacement with balloon-expandable valve : Analysis of initial experience in China.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is widely applied for the treatment of severe aortic stenosis (AS) in developed countries; however, in China, it is still in the early stage of utilization. On the basis of previous studies, this work explored the feasibility of TAVR in patients with severe AS in China and analyzed the cause of death in four cases. METHODS: This retrospective study included 20 patients who had severe AS and underwent TAVR with a balloon-expandable system (Edwards SAPIEN XT) in our hospital from January 2011 to June 2016. The valve and heart functions of 16 survivors before and after the TAVR procedure were compared. TAVR endpoints, device success, and adverse events were assessed according to the definitions of the Valve Academic Research Consortium-2 (VARC-2). RESULTS: There were 13 male and seven female patients aged 65-81 years (average, 73.15) who underwent TAVR. The TAVR approach was transfemoral in 19 patients and transapical in one patient. Four patients died (two of coronary artery occlusion and two of aortic annulus rupture) during the TAVR procedure or shortly after; six patients had mild paravalvular leakage, and the rest of the patients showed a significant improvement in cardiac function. During the follow-up period (2-62 months), one patient died of lung cancer 13 months after the TAVR procedure. CONCLUSION: TAVR with a balloon-expandable system is safe and effective and can be used for patients with severe AS in China. It requires careful patient selection and preoperative assessment so as to reduce the 30-day postoperative mortality rate.