Reference intervals of biochemical analytes in healthy adults from northern China: A population-based cross-sectional study.

Reference intervals (RIs) of laboratory testing play a fundamental role in medical activities. RIs vary greatly for populations in different areas This study aimed to evaluate the age- and sex-specific reference intervals for a healthy population in a typical city of northern China. A cross-sectional study was performed in 4 tertiary care centers of Shijiazhuang of China, biochemical analytes were analyzed using a Beckman Coulter AU5800 (Beckman Coulter Inc., Brea, CA). A total of 42,979 healthy individuals were involved in this study. Grouped by age- and sex-specific, reference intervals of all the measures have been established. We found that different age groups of males and females have significant differences (all P < .001) in levels of various biochemical analytes. We provided a comprehensive age- and sex-specific RIs for biochemical analytes, which showed dynamic changes with both age and sex. For the local population, the reference intervals established here can be adopted in other clinical laboratories after appropriate validation.

Rational discovery of dual FLT3/HDAC inhibitors as a potential AML therapy.

Acute myeloid leukemia (AML) patients often experience poor therapeutic outcomes and relapse after treatment with single-target drugs, representing the urgent need of new therapies. Simultaneous inhibition of multiple oncogenic signals is a promising strategy for tumor therapy. Previous studies have reported that concomitant inhibition of Fms-like tyrosine kinase 3 (FLT3) and histone deacetylases (HDACs) can significantly improve the therapeutic efficacy for AML. Herein, a series of novel dual FLT3/HDAC inhibitors were developed through a rational structure-based drug design strategy for the first time. Among them, multiple compounds showed potent and equivalent inhibitory activities against FLT3-ITD and HDAC1, with the representative compound 63 selectively inhibiting HDAC class I (HDAC1/2/3/8) and IIB isoforms (HDAC6) related to tumorigenesis, and intensively blocking proliferation of MV4-11 cells. The antiproliferation activity was proven to depend on the dual inhibition of FLT3 and HDAC1. Mechanism assays demonstrated that 63 prohibited both FLT3 and HDAC pathways, induced apoptosis and arrested cell cycle in MV4-11 cells in a dose-dependent manner. In summary, this study validated the therapeutic potential of a kind of dual FLT3/HDAC inhibitors for AML and provided novel compounds for further biological investigation on concomitant inhibition of FLT3/HDAC pathways. Additionally, the structure-based drug design strategy described herein may provide profound enlightenment for developing superior anti-AML drugs.

Hydrophobic tag-based protein degradation: Development, opportunity and challenge.

Targeted protein degradation (TPD) has emerged as a promising approach for drug development, particularly for undruggable targets. TPD technology has also been instrumental in overcoming drug resistance. While some TPD molecules utilizing proteolysis-targeting chimera (PROTACs) or molecular glue strategies have been approved or evaluated in clinical trials, hydrophobic tag-based protein degradation (HyT-PD) has also gained significant attention as a tool for medicinal chemists. The increasing number of reported HyT-PD molecules possessing high efficiency in degrading protein and good pharmacokinetic (PK) properties, has further fueled interest in this approach. This review aims to present the design rationale, hydrophobic tags in use, and diverse mechanisms of action of HyT-PD. Additionally, the advantages and disadvantages of HyT-PD in protein degradation are discussed. This review may help inspire the development of more HyT-PDs with superior drug-like properties for clinical evaluation.

Proximal tibia osteotomy with absorbable spacer combined with fibular osteotomy versus high tibial osteotomy for medial compartmental knee osteoarthritis.

PURPOSE: The study aimed to compare the perioperative complications, short-term clinical outcomes, patient-reported outcomes, and radiographic parameters of tibiofibular proximal osteotomy combined with absorbable spacer insertion (TPOASI) and open-wedge high tibial osteotomy (OWHTO) in a two year postoperative time period. METHODS: A total of 160 patients with Kellgren-Lawrence classification grade 3 medial compartmental knee OA were randomized to receive either TPOASI (n = 82) or OWHTO (n = 78). The primary and secondary outcomes were measured preoperatively, postoperatively, and at each follow-up examination. The primary outcomes were the between-group change in the Western Ontario and McMaster Universities Global score (WOMAC). Secondary measures included visual analog scale (VAS), radiographic parameters, American Knee Society Score (KSS), operation time, blood loss, length of incision, hospital stay, and relevant complications. Postoperative radiographic parameters, including the femorotibial angle (FTA), varus angle (VA), and joint line convergence angle (JLCA), were measured to evaluate the correction of varus deformity. RESULTS: No significant differences were found in the baseline data between the two groups. Both methods improved functional status and pain postoperatively. For primary outcomes of both groups, statistical difference was observed in WOMAC scores at the 6-month follow-up (P < 0.001). For secondary outcomes, no statistical difference was observed between the groups during the 2-year follow-up (P > 0.05). For TPOASI vs. OWHTO, the mean hospital stay (6.6 ± 1.3 days vs. 7.8 ± 2.1 days) was shorter (P < 0.001), and both blood loss (70.56 ± 35.58 vs. 174.00 ± 66.33 mL) and complication rate (3.7% vs. 12.8%) were significantly lower (P < 0.005 for both). CONCLUSIONS: Both approaches showed satisfactory functional outcomes and alleviated pain. However, TPOASI is a simple, feasible method with few complications, and it could be widely used.

Hydroamination of Unactivated Alkenes with Aliphatic Azides.

We report here an efficient and highly diastereoselective intermolecular anti-Markovnikov hydroamination of unactivated alkenes with aliphatic azides in the presence of silane. The system tolerates a wide range of azides and alkenes and operates with alkene as limiting reagent. Mechanistic studies suggest a radical chain pathway that involves aminium radical formation, radical addition to alkenes and HAT from silane to ß-aminium alkyl radical. The use of sterically bulky silane is proposed to contribute to the excellent diastereoselectivity for HAT. Computational analysis uncovers the reaction pathway of aliphatic azide activation with silyl radical for aminyl radical formation.

National incidence of joint dislocation in China: a retrospective survey of 512,187 individuals.

BACKGROUND: Joint dislocations significantly impact public health. However, a comprehensive study on the incidence, distribution, and risk factors for joint dislocations in China is lacking. We conducted the China National Joint Dislocation Study, which is a part of the China National Fracture Study conducted to obtain the national incidence and risk factors for traumatic fractures, and to investigate the incidence and risk factors for joint dislocations. METHODS: For this national retrospective epidemiological study, 512,187 participants were recruited using stratified random sampling and probability-proportional-to-size method from January 19 to May 16, 2015. Participants who sustained joint dislocations of the trunk, arms, or legs (skull, sternum, and ribs being excluded) in 2014 were personally interviewed to obtain data on age, educational background, ethnic origin, occupation, geographic region, and urbanization degree. The joint-dislocation incidence was calculated based on age, sex, body site, and demographic factors. The risk factors for different groups were examined using multiple logistic regression. RESULTS: One hundred and nineteen participants sustained 121 joint dislocations in 2014. The population-weighted incidence rate of joint dislocations of the trunk, arms, or legs was 0.22 (95% confidence interval [CI]: 0.16, 0.27) per 1000 population in 2014 (men, 0.27 [0.20, 0.34]; women, 0.16 [0.10, 0.23]). For all ages, previous dislocation history (male: OR 42.33, 95% confidence interval [CI]: 12.03-148.90; female: OR 54.43, 95% CI: 17.37-170.50) and alcohol consumption (male: OR 3.50, 95% CI: 1.49-8.22; female: OR 2.65, 95% CI: 1.08-6.50) were risk factors for joint dislocation. Sleeping less than 7 h/day was a risk factor for men. Compared with children, women aged ≥15 years (female 15-64 years: OR 0.16, 95% CI: 0.04-0.61; female ≥65 years: OR 0.06, 95% CI: 0.01-0.41) were less likely to sustain joint dislocations. Women with more than three children were at higher dislocation risk than women without children (OR 6.92, 95% CI: 1.18-40.78). CONCLUSIONS: The up-to-date data on joint dislocation incidence, distribution, and risk factors can be used as a reference for national healthcare, prevention, and management in China. Specific strategies for decreasing alcohol consumption and encouraging adequate sleeping hours should be developed to prevent or reduce dislocation incidents. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-EPR-15005878.

Relative Prevalence and Associated Factors of Complex Regional Pain Syndrome Type I in Patients with Radial Head Fractures Treated with Open Reduction and Internal Fixation: A Cross-Sectional Study.

Objective: This cross-sectional study aimed to examine the incidence and associated factors of complex regional pain syndrome type I (CRPS I) in patients who underwent open reduction and internal fixation (ORIF) for radial head fractures. Methods: The study enrolled 601 radial head fracture patients treated with ORIF, 523 of which completed the 1-year follow-up. The incidence of CRPS I in those patients was assessed using the Budapest criteria. Patients were then divided into 2 groups: patients with CRPS I (n = 28) and patients without CRPS I (n = 495). The patients' demographic and clinical data before the operation were prospectively collected by our team. Independent t-tests and χ 2 tests were used as univariate analyses to compare the demographic and clinical data between the two groups. Meanwhile, multivariate regression analysis was conducted to identify the associated risk factors for CRPS I. Results: The incidence of CRPS I in patients with radial head fractures treated with ORIF was 5.5% during the first year following surgery. Significant differences were observed in age, gender, type of trauma, modified Mason Classification, and depressive personality disorders. The logistic regression analysis revealed that the female gender, modified Mason type III fractures, and depressive patients were significantly more likely to develop CRPS I (p=0.021, 0.023, and 0.025, respectively). Conclusions: The incidence of CRPS I among radial head fracture patients undergoing ORIF was 5.5%. In addition, early detection of CRPS I and providing adequate intervention will likely result in greater benefits for those patients.

Design of 1-Phosphanorbornene Derivatives as Chiral Organocatalysts for Enantioselective (4 + 2) Annulation Reactions of γ-Benzyl Allenoates.

Two novel diastereoisomeric P-chirogenic phosphine catalysts, i.e., JiaPhos, which can be easily derived from inexpensive and commercially available starting materials in five chemical operations (totally 4.16g scale), are introduced. To our delight, the JiaPhos catalysts display good performance in enantioselective (4 + 2) annulations involving 3-methylene-2-oxindoles and γ-benzyl allenoates, providing a wide range of 3,3'-spirocyclic oxindoles with good efficiency and enantioselectivity.

Determinants of anxiety and depression among pheochromocytoma patients: A case-control study.

ABSTRACT: Phaeochromocytomas are catecholamine-producing neuroendocrine tumors that may manifest in many ways, specifically as sustained or paroxysmal hypertension. Data, including data from mental status screening, were prospectively collected from suspected patients. The Hospital Anxiety and Depression Scale was used as a screening tool to identify abnormal mental status. Results showed phaeochromocytoma patients were more likely to experience anxiety and depression. For future phaeochromocytoma treatment, early screening for anxiety and depression should be recommended.

Relative Prevalence of and Factors Associated with Anxiety and Depression in Degenerative Triangular Fibrocartilage Complex Lesion Patients - a Casecontrol Study.

Triangular fibrocartilage complex (TFCC) lesions are a common cause of ulnar wrist pain. Data, including mental status assessment, were prospectively collected from patients who underwent arthroscopy. The HADS was used to assess the prevalence of depression and anxiety. Patients with degenerative TFCC lesions were at an increased risk of anxiety and depression. Early screening for anxiety and depression in degenerative TFCC lesions patients should be recommended.

Determinants of anxiety and depression in patients with cubital tunnel syndrome.

BACKGROUND: The aim of this cross-sectional study to assess the proportions of anxiety and depression in patients with CuTS, and to explore the associated demographic and clinical features. METHODS: From May 2011 to January 2017, 246 patients diagnosed with CuTS were recruited. The Hospital Anxiety and Depression Scale was used to assess the proportions of depression and anxiety. Patient demographic and clinical data were collected. Univariate analysis and multivariate regression were carried out to identify the variables that were independently associated with anxiety and depression. RESULTS: The proportions of depression and anxiety were 17.9% (n = 44) and 14.2% (n = 35), respectively. Five patients had both possible/probable anxiety and depression. Logistic regression analysis revealed that diabetes mellitus was independently associated with depression; and the modified McGowan grade was independently associated with anxiety. CONCLUSIONS: In patients with CuTS, the proportions of depression and anxiety were 17.9% and 14.2%, respectively. Early screening for anxiety and depression is beneficial for patients with CuTS.

Phosphine/Palladium Cooperative Catalysis: (4 + 3) Annulations of Morita-Baylis-Hillman Carbonates and Vinyl Benzoxazinanones.

A novel (4 + 3) annulation reaction of Morita-Baylis-Hillman carbonates and vinyl benzoxazinanones has been developed by using phosphine/palladium dual catalysis. This reaction demonstrates a wide substrate scope, providing a range of vinyl 2, 3-dihydro-1H-benzo[b]azepine derivatives in moderate to good yields and diastereoselectivities. Experimental results indicate that both palladium and phosphine play crucial roles in the annulation reactions.