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Objective: To explore the relationship between insomnia and osteoporosis. Methods: Mendelian randomization (MR) analysis were used in this study. The single nucleotide polymorphisms (SNPs) related to insomnia from genome-wide association analysis research data were selected as the instrumental variables by using inverse variance weighted (IVW), MR-Egger regression, weighted median method, maximum likelihood, penalized weighted median estimator, and Mendelian randomization robust adjusted profile score (MR-RAPS) to determine the causal relationship between insomnia and osteoporosis. Odds ratio ( OR ) and 95% confidence interval ( CI ) values were used to evaluate the association between insomnia and osteoporosis. Cochran's Q -test was used to detect heterogeneity of SNPs, MR-Egger regression was used to test for level pleiotropy, and the leave-one-out method was used to test sensitivity, MR pleiotropy residual sum and outlier (MR-PRESSO) method and radial MR were used to detect erroneous outliers. Results: The screening criteria were set based on the three major assumptions of MR; finally, 31 SNPs were included in the MR analysis. The results of MR causal effect analysis using the IVW method showed that insomnia increased the risk of osteoporosis by about 0.7% ( OR =1.007, 95% CI 1.001-1.014, P =0.044); heterogeneity testing showed heterogeneity between SNPs ( Q =57.91, P <0.001); and the MR- Egger intercept test did not indicate horizontal pleiotropy in this study (intercept value=3.807×10 -5 , P =0.888). Leave-one-out method showed that no single SNP had a significant impact on the overall results. No abnormal SNP was detected according to the MR-PRESSO results ( P =0.059), and radial MR did not detect any outliers. Conclusion: Mendelian randomization analysis showed that insomnia can increase the risk of osteoporosis.

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.

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.

Objective: Changes in hormone levels, improper lipid metabolism, and oxidative stress all significantly contribute to the pathogenic process of polycystic ovarian syndrome (PCOS). According to earlier research, pioglitazone and alpha-lipoic acid are crucial in the emergence of PCOS. The beneficial effects of pioglitazone and alpha-lipoic acid on PCOS were examined in the current study., Patients and Methods: The 120 patients with PCOS received three months of treatment in pioglitazone groups (n=40 case, 30 mg/time, 1 time/day), α-lipoic acid (n=40 case, 0.6 g/time, 1 time/day), and combination therapy (n=40 case, pioglitazone 30 mg/time, 1 time/day and α-lipoic acid, 0.6 g/time, 1 time/day). Before and after therapy, the following factors were evaluated: the hormonal profile, fasting serum insulin, body weight, body mass index (BMI), menstruation status, oxidative stress, and indications of lipid metabolism., Results: The combination of pioglitazone and α-lipoic acid has a significantly improving effect on BMI, body weight, oxidative stress levels, lipid metabolism, and menstrual status. A significant increase in body weight, BMI, and follicle-stimulating hormone (FSH) levels were found in mice after being treated with α-lipoic acid alone. However, the use pioglitazone alone improves body weight, BMI, the calculation of insulin resistance index (HOMA-IR), Area under the curve (AUC)-insulin, fasting glucose/insulin (G/I) ratio, total testosterone, and malondialdehyde (MDA) levels in post-treatment than pre-treatment., Conclusions: These findings suggest that pioglitazone alone has a better effect than alpha-lipoic acid in improving oxidative stress levels, BMI, and menstrual cyclicity. Additionally, treatment with pioglitazone and alpha-lipoic acid did demonstrate a greater effect than monotherapy with each medication alone.

Background: Despite the prolonged median disease-free survival (DFS) by adjuvant targeted therapy in non-small-cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations, the relationship between the treatment duration and the survival benefits in patients remains unknown., Patients and Methods: In this multicenter, randomized, open-label, phase II trial, eligible patients aged 18-75 years with EGFR-mutant, stage II-IIIA lung adenocarcinoma and who had not received adjuvant chemotherapy after complete tumor resection were enrolled from eight centers in China. Patients were randomly assigned (1 : 1) to receive either 1-year or 2-year icotinib (125 mg thrice daily). The primary endpoint was DFS assessed by investigator. The secondary endpoints were overall survival (OS) and safety. This study was registered at ClinicalTrials.gov (NCT01929200)., Results: Between September 2013 and October 2018, 109 patients were enrolled (1-year group, n = 55; 2-year group, n = 54). Median DFS was 48.9 months [95% confidence interval (CI) 33.1-70.1 months] in the 2-year group and 32.9 months (95% CI 26.6-44.8 months) in the 1-year group [hazard ratio (HR) 0.51; 95% CI 0.28-0.94; P = 0.0290]. Median OS for patients was 75.8 months [95% CI 64.4 months-not evaluable (NE)] in the 2-year group and NE (95% CI 66.3 months-NE) in the 1-year group (HR 0.34; 95% CI 0.13-0.95; P = 0.0317). Treatment-related adverse events (TRAEs) were observed in 41 of 55 (75%) patients in the 1-year group and in 36 of 54 (67%) patients in the 2-year group. Grade 3-4 TRAEs occurred in 4 of 55 (7%) patients in the 1-year group and in 3 of 54 (6%) patients in the 2-year group. No treatment-related deaths or interstitial lung disease was reported., Conclusions: Two-year adjuvant icotinib was shown to significantly improve DFS and provide an OS benefit in EGFR-mutant, stage II-IIIA lung adenocarcinoma patients compared with 1-year treatment in this exploratory phase II study., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Recently, accumulating evidence has shown that hydrogen sulphide (H 2 S), a newly determined gasotransmitter, plays important roles in senescence, which is an essential biological process for plant fitness and an important agricultural trait that is critical for the yield and quality of farm produce. Here, in this review, we summarize the roles of H 2 S in senescence, both before and after the harvesting of agricultural products, and the underlying mechanism is also discussed. During the plant growth process, the function of H 2 S in the leaf senescence process has been studied extensively, and H 2 S plays roles during the whole process, including the initiation, reorganization and terminal stages. While during the postharvest stage, H 2 S can prevents farm products from deterioration resulting from over-ripening, pathogen attack and incorrect storage. The underlying H 2 S-related mechanisms during different stages of the senescence process are summarized and compared. The most prominent interaction occurs between H 2 S and reactive oxygen species, and the molecular mechanism is explored. Additionally, the conserved action mode of H 2 S in different life processes and different species is also discussed. In the future, multi-omics analyses over time will be needed to investigate the detailed mechanisms of H 2 S, and a safety attribute analysis of H 2 S is also required before it can be used in agricultural production., (© 2021 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.)

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.

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.

The aim of this study was to develop an integrative framework on aging, immigration, and oral health. The methodology was a critical review that used immigration as a social determinant framework through which to evaluate its impact on the oral health of older immigrants. We reviewed recent empirical evidence on factors related to oral health in older immigrants. In a systematic search across multiple databases, we identified 12 eligible studies in this review. Among the eligible studies, most were conducted among East Asian immigrants (8 articles), followed by non-Hispanic White/European origin (2 articles), Mexican origins (1 article), and Iran and other Middle East regions (1 article). The research revealed knowledge gaps in the evidence base, including the dynamic relationship between acculturation and oral health, the role of environmental factors on oral health for immigrants, psychosocial stressors and their relationship with oral health, and oral health literacy, norms, and attitude to dental care utilization and oral hygiene practices. The development of the integrative framework suggests the pathways/mechanisms through which immigration exerts influences on oral health in later life. This provides opportunities for researchers, practitioners, and policy makers to gain greater insights into the complex associations between immigration and oral health among older adults.

Objectives: Bedaquiline treatment significantly improves multidrug-resistant tuberculosis (MDR-TB) patient treatment outcomes. However, safety and efficacy data are lacking for bedaquiline used with background regimens to treat Chinese TB patients. Here, we describe our initial clinical experience for bedaquiline treatment of a large multicentre cohort of MDR-TB and extensively drug-resistant tuberculosis (XDR-TB) patients in China., Methods: Patients (177) received 24-week bedaquiline treatment combined with personalized anti-TB drug background regimens. As primary efficacy endpoints, times to initial sputum culture conversion were measured., Results: Of 177 MDR-TB patients completing the 24-week treatment course, sputum culture conversion occurred for 151/177 (85.3%), while 26 had unfavourable outcomes, including 3/177 (1.7%) deaths and 23/177 (13.0%) non-responders at treatment completion. The median time to sputum culture conversion was 4 (interquartile range 2-8) weeks. Conversion rates were 33/39 (84.6%, 95% confidence interval (CI) 73.3-95.9) for MDR-TB patients, 47/56 (83.9%, 95% CI 74.3-93.6) for pre-XDR-TB patients and 71/82 (86.6%, 95% CI 79.2-94.0) for XDR-TB patients. Multivariate analysis demonstrated that patients with low body mass index (odds ratio 7.356; 95% CI 2.652-20.401) were at significantly high risk of unfavourable outcomes, with serious adverse events noted in 15 (8.5%) patients, including six with corrected QT interval (QTc) prolongation times (>500 ms)., Conclusion: Bedaquiline, when included in background regimens for treatment of MDR-TB and XDR-TB patients in China, was safe and associated with a high rate of culture conversion., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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.

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., (Copyright © 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

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.

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.

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.

Background: Obesity is strongly associated with insulin resistance and elevated plasma glucose levels. The rs9356744 polymorphism in the CDKAL1 gene is associated with body mass index (BMI) only in East Asians. Here, we examined the effect of the rs9356744 polymorphism on glucose-related traits and prediabetes in Chinese adults., Methods: A total of 2 357 participants were enrolled from the Cardiometabolic Risk in Chinese (CRC) Study, including 499 persons with prediabetes, 204 persons with type 2 diabetes, and 1 654 normoglycemic controls. The rs9356744 polymorphism in CDKAL1 was genotyped and analyzed in all participants., Results: Despite the positive relationship between obesity and glucose traits, the T allele of rs9356744, which is associated with a predisposition to obesity, was correlated with lower levels of 2-h oral glucose tolerance test (OGTT) plasma glucose (2hPG) (β=- 0.2104 and P =0.0233), glycated hemoglobin (HbA1c) (β=- 0.0551 and P =0.0298) and higher levels of homeostasis model of assessment β-cell function (HOMA-B) (β=5.282 and P =0.0424). After further adjustment for BMI, the levels of HOMA-B maintained a similar increased trend across rs9356744 genotype (β=3.277 and P =0.1958). In stratified analyses, the associations of rs9356744 with 2hPG and HbA1c were significant for individuals with a low BMI. Moreover, an antagonism action of BMI and rs9356744 on 2hPG ( P for interaction=0.0055) was observed. In addition, we found a protective effect of rs9356744 on prediabetes., Conclusions: The CDKAL1 rs9356744 T allele associated with a predisposition to obesity showed a protective effect on HbA1c, 2hPG, and prediabetes. BMI was mediator of the association between the genetic variant and HbA1c, 2hPG, and prediabetes., Competing Interests: Jun Liang, Yan Zhu, Xue-Kui Liu, Qin-Qin Qiu, Yu-Ting Sun, Yu Wang, Ying Pei, and Man-Qing Yang declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To analyze clinical features, prognosis and treatment of lymphocytic hypophysitis (LYH). Methods: The clinical data, treatments and outcomes of 18 cases diagnosed as LYH at Chinese PLA General Hospital between January 2001 and July 2017 was respectively reviewed. Results: Eighteen patients with histology-proven LYH (13 females and 5 males ) were identified. All lymphocytic adenohypophysitis (LAH) were females( n =6), two of whom were associated with pregnancy. Eleven patients (6 females and 5 males) had lymphocytic panhypophysitis (LPH) and one(female) had hypothalamitis. Pre-treatment evaluation revealed that 11 patients presented with symptoms of intracranial space-occupying lesions, 12 patients had symptoms of anterior pituitary hormone deficiencies, and 12 patients had central diabetes insipidus (CDI). All patients had space-occupying lesions on magnetic resonance imaging (MRI), which were symmetrically enlarged and homogenously enhanced with or without pituitary stalk thickening. Before or after surgery, 11 patients received immunosuppressant therapy or radiotherapy to alleviate space-occupying effect. After 4-204 months follow-up, 5 patients had a relapse and received immunosuppressants, radiotherapy or surgery to achieve remission. Full recovery (both symptomatic and radiographic) was seen in 6 patients, and 11 patients maintained stable replacement therapy. Conclusions: LYH presents with acute space-occupying effects such as headache, visual disturbances, hypopituitarism, CDI and mild hyperprolactinemia, especially with characteristic radiographic manifestations. Usually, surgery reliably establishes diagnosis, and immunosuppressant therapy is a necessity. On the whole, LYH has a good prognosis.

Objective: To summarize and analyze the clinical features and etiologies in hospitalized patients with syndrome of inappropriate antidiuretics (SIAD) during the past 25 years. Methods: All data of 128 patients with SIAD admitted to Chinese PLA General Hospital since January 1991 to January 2016 were collected. SIAD was diagnosed based on the 1957 criterion. Results: (1) The most frequent causes of increased inappropriate secretion of vasopressin were malignant tumors, lung diseases (e. g. pneumonia), and central nervous system diseases, in which malignant tumors accounted for 38.28% of the SIAD. (2) During the past 25 years, the proportion of malignant diseases declined from 4/7 to 35.29%, while, the proportion of pulmonary infection increased from 1/7 to 35.29% ( P <0.05). (3) The patients with malignant tumors had the lowest serum sodium and serum osmolality among all SIAD patients. (4) CT scan had a high diagnostic value for chest and brain detection. (5) Among three SIAD subjects with unknown reasons at onset, two were diagnosed with small cell lung cancer and one with gastric cancer during follow-up. Conclusion: The etiology of SIAD is complex and it could be attributed to multifarious etiological factors. Malignant tumors account for the largest proportion of all patients, and pulmonary infection was ranked in second place. Cautions on tumors have to be taken when serum sodium of a SIAD patient is below 118.1 mmol/L.

In a random sample of postmenopausal Chinese women, the prevalence of radiographic vertebral fractures increased from 13% between ages 50 and 59 to over 50% after age 80 years. A model with seven clinical risk factors predicted the probability of vertebral fractures as well with as without BMD and better than a model with only three risk factors. More than half an hour of outdoor activity per day might correlate with lower risk of vertebral fracture in this population., Introduction: We aimed to describe the prevalence and develop a model for prediction of radiographic vertebral fractures in a large random sample of postmenopausal Chinese women., Methods: We enrolled 1760 women from an age-stratified random sample of postmenopausal women in Beijing, China. The presence of vertebral fracture was assessed by semi-quantitative grading of lateral thoracolumbar radiographs, risk factors by interview, bone mineral density (BMD) of the proximal femur and lumbar spine by dual x-ray absorptiometry (DXA), and markers of bone turnover from a fasting blood sample. Associations of these factors were analyzed in logistic models and discrimination by areas of receiver operating characteristics curves (AUC)., Results: The prevalence of vertebral fracture, ranged from 13.4% ages 50 to 59 years old to 58.1% at age 80 years or older. Older age, a history of non-vertebral fracture, lower femoral neck BMD T-score, body mass index (BMI), height loss, housework, and less than half an hour of outdoor activity were significantly associated with increased probability of having a vertebral fracture. A model with those seven factors had a similar AUC with or without BMD and performed better than a simple model with three factors., Conclusion: This study is from a true random sample of postmenopausal women in urban China with high response rate. The prevalence of vertebral fractures in postmenopausal women in Beijing increases from 13% under age 60 to over 50% by age 80 years. A model with seven clinical risk factors with or without BMD is better than simple models and may guide the use of spine x-rays to identify women with vertebral fractures. More than half an hour of outdoor activity might correlate with lower risk of vertebral fracture in this population.

Cryptorchidism is one of the most common congenital anomalies and affects 2-4% of full-term new born boys. Its aetiology is poorly understood at present. HOXA10 plays a pivotal role in regulation of testicular descent. Male mice mutant for Hoxa10 exhibit unilateral or bilateral cryptorchidism as a result of impaired development of the gubernaculums. In this study, we performed mutation analysis of HOXA10 gene in a cohort of 98 cryptorchid patients. And we found a mutation (N27K) in a boy with unilateral cryptorchidism. The mutation was not detected in 106 healthy controls. Both in silico analyses and functional studies showed that the mutation affected the function of HOXA10. The results demonstrated that mutation in HOXA10 gene contributes to the pathogenesis of cryptorchidism, but may not be a common cause., (© 2016 Blackwell Verlag GmbH.)

The c-Jun NH2-terminal protein kinase (JNK) pathway has been implicated in mammary tumor development. However, the molecular mechanisms regulating JNK activity in breast cancer cells remain unclear. Here, we report that the inhibition of ubiquitination-like post-translational modification neddylation through different strategies results in enhanced basal JNK phosphorylation in human breast cancer cells. The upregulation of basal JNK phosphorylation upon neddylation inhibition is independent of the deneddylation of Cullins, the well-characterized neddylation substrates. Since augmented basal JNK phosphorylation via ectopic MKK7 expression impedes proliferation and the epithelial-to-mesenchymal transition (EMT) phenotype, the neddylation system might contribute to mammary tumor development partially through limiting basal JNK phosphorylation. Further exploration reveals that MKK7, a JNK-specific MAP2K, undergoes neddylation in human breast cancer cells. MKK7 co-precipitates with a fragment of Ran-binding protein 2 (RanBP2), a large multimodular and pleiotropic protein that has been recognized as a SUMO E3 ligase. Knockdown of RanBP2 attenuates MKK7 neddylation and augments basal JNK phosphorylation without affecting the neddylation of Cullins, whereas ectopic expression of a RanBP2 fragment possessing SUMO E3 activity (RanBP2ΔFG) manifests the opposite effects. In vitro neddylation assays confirm that RanBP2ΔFG works as the neddylation E3 ligase for MKK7. The basal kinase activity of endogenous MKK7 increases upon RanBP2 knockdown but decreases upon the ectopic expression of RanBP2ΔFG. Furthermore, purified MKK7 shows reduced basal kinase activity after in vitro neddylation by RanBP2ΔFG. Consistently, RanBP2 knockdown leads to reduced proliferation and impaired EMT phenotype in human breast cancer cells and the effects of RanBP2 knockdown are reversed by simultaneous MKK7 knockdown. Taken together, our data suggest that MKK7 undergoes neddylation in human breast cancer cells, which limits its basal kinase activity.

Objective: The causal relationship between serum uric acid (SUA) level and non-alcoholic fatty liver disease (NAFLD) has not yet been clarified. The objective of the study was to determine the association between SUA and NAFLD, as well as assess the interactions between SUA and other metabolic risk factors regarding NAFLD., Patients and Methods: The study samples related to a community-based health examination survey conducted in Central China. Initially, a total of 24,878 patients with medical examination were included. After excluding the individuals with confounding factors, the remaining 21,798 subjects with biomarkers available were included in the present study., Results: The data show that the risk of NAFLD significantly increased with the elevated SUA levels. Further adjustments for sex, age, and other confounding metabolic factors did not change the increasing trend of NAFLD risk. The odds ratios [ORs, 95% confidence interval (CI)] of NAFLD across the increasing quintiles of SUA were 1.00, 1,530 (1.174-1.995), 2.24 (1.714-2.886), 2.636 (2.019-3.441), and 3.714 (2.828-4.877) (p for trend < 0.0001). Also, significant interaction was found between SUA and prehypertension in relation to the NAFLD risk (p for interaction < 0.05)., Conclusions: SUA was significantly associated with NAFLD risk, independent of other metabolic risk factors, and SUA also had significant interaction with prehypertension regarding the risk of NAFLD.

Although three-dimensional (3-D) porous regenerated silk scaffolds with outstanding biocompatibility, biodegradability and low inflammatory reactions have promising application in different tissue regeneration, the mechanical properties of regenerated scaffolds, especially suture retention strength, must be further improved to satisfy the requirements of clinical applications. This study presents woven silk fabric-reinforced silk nanofibrous scaffolds aimed at dermal tissue engineering. To improve the mechanical properties, silk scaffolds prepared by lyophilization were reinforced with degummed woven silk fabrics. The ultimate tensile strength, elongation at break and suture retention strength of the scaffolds were significantly improved, providing suitable mechanical properties strong enough for clinical applications. The stiffness and degradation behaviors were then further regulated by different after-treatment processes, making the scaffolds more suitable for dermal tissue regeneration. The in vitro cell culture results indicated that these scaffolds maintained their excellent biocompatibility after being reinforced with woven silk fabrics. Without sacrifice of porous structure and biocompatibility, the fabric-reinforced scaffolds with better mechanical properties could facilitate future clinical applications of silk as matrices in skin repair., (Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Genetic factors have been shown to play a role in the development of head and neck cancers (HNCs). However, studies investigating the association between the TP53 Arg72Pro polymorphism and HNCs susceptibility have yielded conflicting results. Hence, we performed a meta-analysis of all eligible studies (up to January 1, 2012) to derive a more precise estimation of this association in order to increase understanding of the possible risk factors of HNCs. Twenty-seven case-control studies involving 3966 cases and 4387 controls were included in our analysis. Overall, no evidence of association was observed between the TP53 Arg72Pro single nucleotide polymorphism (SNP) and the risk of HNCs in any genetic model (Arg/Arg vs Pro/Pro: odds ratio (OR) = 0.83, 95% confidence interval (CI): 0.65-1.06; Arg/Pro vs Pro/Pro: OR = 0.88, 95%CI= 0.70-1.10; Arg/Arg+Arg/Pro vs Pro/Pro: OR = 0.87, 95%CI= 0.70-1.09; Arg/Arg vs Arg/Pro+Pro/Pro: OR = 0.95, 95%CI= 0.82-1.11). Nevertheless, the TP53 Arg72Pro polymorphism shows diverse effects across different subtypes of HNCs. For example, there was a lack of association of this polymorphism with oral cavity cancer, whereas a significant association with nasopharyngeal cancer was observed. Results of this meta-analysis suggest that the TP53 Arg72Pro polymorphism might have different effects on the risk of various subtypes of HNCs.

In this paper, we propose a simultaneous design method of motion and external force trajectories for knee joint rehabilitation based on the biomechanical analysis of the lower limb. In this method we assume to use two robots manipulators which provide forces and moments at shank and thigh. We developed a 7 degree of freedom musculoskeletal model of lower limb with 19 muscles. The valuation function of rehabilitation efficiency e has been maximized by Genetic Algorithm (GA) that refers to the musculoskeletal model and tunes motion trajectory of the robots and forces acting on the shank and thigh.

In the Traditional Chinese Medicine (TCM) cross-sectional survey conducted by our team, we were interested in determining the risk factors of osteoporosis. To analyze this TCM study, we had to deal with three statistical problems: (1) a very large number of potential risk factors, (2) interactions among potential risk factors, and (3) nonlinear effects of some continuous-scale risk factors. To address these analytic issues, we used two data mining methods, support vector machine recursive feature elimination and random forest; to deal with the curse of high-dimensional risk factors, we applied another data mining technique of association rule learning to discover the potential associations among risk factors. Finally, we employed the generalized partial linear model (GPLM) to determine nonlinear effects of an important continuous-scale risk factor. The final GPLM model shows that TCM symptoms play an important role in assessing the risk of osteoporosis. The GPLM also reveals a nonlinear effect of the important risk factor, menopause years, which might be missed by the generalized linear model., (Copyright © 2012 John Wiley & Sons, Ltd.)

In this paper, we propose a simultaneous design method of motion and external force trajectories for shoulder inner muscles in the robot-aided rehabilitation system, based on a biomechanical analysis of patient's body. The rehabilitation efficiency evaluation function was maximized by Genetic Algorithm (GA), where the structure of spline curves parameters are pre-defined, and the structural parameters are explored to design smooth rehabilitation motion and external force trajectories.

We introduce a method for lower-limb physical rehabilitation by means of a robot that applies preliminary defined forces to a patient's foot while moving it on a preliminary defined trajectory. We developed a special musculoskeletal model that takes into consideration the generated muscle forces of 27 musculotendon actuators and joint stiffness of the leg and allows the calculation of the motion trajectory of the robot and the forces that the robot needs to apply to the foot in each moment of the therapeutic exercise. Robotic treatment programs are customized for the individual patient by using a genetic algorithm (GA) that refers to the musculoskeletal model and calculates the parameters of the spline curves of the motion trajectory of the robot and forces acting on the foot.

DNA copy number analysis was performed, using single-nucleotide polymorphism mapping arrays, to fine map genomic imbalances in human malignant mesothelioma (MM) cell lines derived from primary tumors. Chromosomal losses accounted for the majority of genomic imbalances. All 22 cell lines examined showed homozygous deletions of 9p21.3, centering at the CDKN2A/ARF and CDKN2B loci. Other commonly underrepresented segments included 1p36, 1p22, 3p21-22, 4q13, 4q34, 11q23, 13q12-13, 14q32, 15q15, 18q12, and 22q12, each observed in 55-90% of cell lines. Focal deletions of 11q23 encompassed the transcriptional repressor gene promyelocytic leukemia zinc finger (PLZF), which was validated by analysis of genomic DNA using real-time polymerase chain reaction (PCR). Semi-quantitative RT-PCR and immunoblot analysis revealed that PLZF is greatly downregulated in MM cell lines compared with non-malignant mesothelial cells. Ectopic expression of PLZF in PLZF-deficient MM cells resulted in decreased cell viability, reduced colony formation, as well as increased apoptosis, the latter based on results of various cell death assays and the observation of increased cleavage of caspase 3, PARP, and Mcl-1. These data indicate that deletions of PLZF are a common occurrence in MM and that downregulation of PLZF may contribute to MM pathogenesis by promoting cell survival.

We report six patients who had dermatitis after contacting certain chemical substances (one worker with contact 1-chloromethyl naphthalene and five with contact Hydroxy-phthalimide). They appeared like drug-induced erythma multiforme, bullosa epidermalysis from the point of contact gradually spreading to the whole body, combining high temperature, digestive system dysfunction, such as liver dysfunction etc. We can call this occupational drug-induced medicamentosa. The course of dermatosis diseases is 1 - 2 months. Hormone and sustaining treatment may be effective. We discuss chemistry substance, clinical presentation, diagnoses, treatment and relevant prognosis.

Three novel low molecular weight (LMW) glutenin subunits from cultivated einkorn (Triticum monococcum L., A(m)A(m), 2n = 2x = 14) were characterized by SDS-PAGE and molecular weights determined by MALDI-TOF-MS. Their coding genes were amplified and cloned with designed AS-PCR primers, revealing three complete gene sequences. All comprised upstream, open reading frame (ORF), downstream and no introns were present. The deduced amino acid sequences showed that all three genes, named as LMW-M1, LMW-M3 and LMW-M5, respectively, belonged to the LMW-i type subunits with the predicted molecular weight between 38.5206 and 38.7028 kDa. They showed high similarity with other LMW-i type genes from hexaploid bread wheats, but also displayed unique features. Particularly, LMW-M5 subunit contained an extra cysteine residue in the C-terminus except for eight conserved cysteines, which resulted from a single-nucleotide polymorphism (SNP) of the T-C transition, namely arginine --> cysteine substitution at position 242 from the N-terminal end. This is the first report that the LMW-i subunit contained nine cysteines residues that could result in a more highly cross-linked and more elastic glutenin suggesting that LMW-M5 gene may associates with good quality properties. In addition, a total of 25 SNPs and one insertions/deletions (InDels) were detected among three LMW-i genes, which could result in significant functional changes in polymer formation of gluten. It is anticipated that these SNPs could be used as reliable genetic markers during wheat quality improvement. The phylogenetic analysis indicated that LMW-i type genes apparently differed from LMW-m and LMW-s type genes and diverged early from the primitive LMW-GS gene family, at about 12.92 million years ago (MYA) while the differentiation of A(m) and A genomes was estimated at 3.98 MYA.

We outline structure-function contributions from our laboratories on protein-RNA recognition events that monitor siRNA length, 5 -phosphate and 2-nucleotide 3 overhangs, as well as the architecture of Argonaute, its externally bound siRNA complex, and Argonaute-based models involving guide-strand-mediated mRNA binding, cleavage, and release.

Mitochondrial DNA (mtDNA) mutations occur naturally in skeletal muscle fibers from aged rhesus macaques. In addition, mtDNA mutations have been observed in germinal vesicle oocytes from fertile monkeys. The goal of this study was to determine whether the rhesus macaque mitochondrial common deletion was present in oocytes and embryos generated by in-vitro embryo production (IVP), as well as in rhesus adult and embryonic stem cell lines. The rhesus common deletion was detected in IVP-generated embryos, three IVP-derived embryonic stem cell lines (ORMES 1, 2 and 7), one in-vivo-derived embryonic stem cell line (R4) and multiple passages of an adult bone marrow stromal cell (BMSC) line. Mitochondrial DNA from an adult adipose stromal cell (ATSC) line was compared with mtDNA from an immortalized line transfected with a retroviral vector expressing telomerase, ATSC-TERT. Multiple passages of the ATSC line harboured a dramatically higher level of the rhesus common deletion than the immortalized ATSC-TERT line. Accumulation of mtDNA mutations in oocytes, embryos and subsequent embryonic stem cell lines, as well as adult stem cell lines, may contribute to mitochondrial dysfunction, and thereby impair ATP production. The authors believe this information establishes a compelling argument for the parallel development of embryonic stem cell technology in non-human primates and humans.

The adenine nucleotide translocase (ANT) is a key component in maintaining cellular energy homeostasis, and has also been implicated in formation of the mitochondrial permeability transition pore. Human ANT-3 was cloned from a human heart cDNA library and expressed as a histidine-tagged fusion protein in the mitochondria of the Trichoplusia ni. cell line. Overexpression resulted in a concomitant decrease in the endogenous ANT content, allowing for the characterization of binding of known ANT ligands to the human protein. Binding affinities for bongkrekic acid (BKA), ADP, and atractyloside (ATR) were measured in mitochondria from the human ANT-3 expressing cell line, and compared to similar preparations from bovine heart mitochondria by use of a novel radioiodinated derivative of ATR. Binding to ANT-3 by the high affinity inhibitors BKA and ATR, as well as the lower affinity natural ligand ADP, was similar to that measured in bovine heart mitochondria, and to that previously reported for mammalian heart mitochondria. Characterizations such as these of human ANT isoforms may lead to drug development for enhanced mitochondrial function and cellular viability.

Previous studies have shown that the maintenance and proliferation of undifferentiated rhesus monkey embryonic stem (rES) cells requires medium supplemented with fetal bovine serum (FBS). Due to the uncharacterized composition and variation in serum nature, the present study aimed to replace the serum-containing medium with a serum-free medium in the rES cell culture. The results showed that after the initial 48-h culture in the routinely used serum-containing medium, rES cells can grow and proliferate for a prolonged period in the serum-free medium composed of DMEM supplemented with a cocktail of BSA, IGF-1, TGF-alpha, bFGF, aFGF, estradiol, and progesterone. rES cells cultured in the serum-free medium maintained high level of alkaline phosphatase activity and OCT4 level. There was no indication of differentiation as judged by the marker gene expression of all three embryonic germ layers and trophoblast. In addition, serum-free culture would not affect the passage capacity and differentiation potential of rES cells. This work will facilitate the future study of induced differentiation of rES cells and other applications.