Study on the efficacy of 3D printing technology combined with customized plates for the treatment of complex tibial plateau fractures.

Background: Anatomical reduction and stable fixation of complex tibial plateau fractures remain challenging in clinical practice. This study examines the efficacy of using 3D printing technology combined with customized plates for treating these fractures.

Methods: We retrospectively analyzed 22 patients treated with 3D printing and customized plates at the Orthopedic Department of the Central Hospital affiliated with Shenyang Medical College from September 2020 to January 2023.

Disappearance of femoral head shortly after femoral neck fracture: a case report and literature review.

This case report describes a woman in her 70s who presented with a 3-month history of hip pain and inability to walk. Upon admission, she was diagnosed with the extremely rare condition of complete femoral head disappearance. A comprehensive examination was conducted to determine the cause and devise an effective treatment strategy, taking the patient's medical history into account.

The combined application of pulsed electromagnetic fields and platelet-rich plasma in the treatment of early-stage knee osteoarthritis: A randomized clinical trial.

Background: This study aims to evaluate the therapeutic efficacy of combined treatment with pulsed electromagnetic fields (PEMFs) and platelet-rich plasma (PRP) injection in improving pain and functional mobility among patients with early-stage knee osteoarthritis (KOA). We hypothesize that this combined therapy can yield superior treatment outcomes.

Methods: Based on the different treatment regimens, we divided 48 patients diagnosed with Kellgren-Lawrence grades I-III KOA into 3 groups: the PRP group, the PEMFs group, and the PRP + PEMFs group.

ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Nab-Paclitaxel in Patients with Advanced Solid Tumors.

Purpose: In preclinical models, glucocorticoid receptor (GR) signaling drives resistance to taxane chemotherapy in multiple solid tumors via upregulation of antiapoptotic pathways. ORIC-101 is a potent and selective GR antagonist that was investigated in combination with taxane chemotherapy as an anticancer regimen preclinically and in a phase 1 clinical trial.

Patients And Methods: The ability of ORIC-101 to reverse taxane resistance was assessed in cell lines and xenograft models, and a phase 1 study (NCT03928314) was conducted in patients with advanced solid tumors to determine the dose, safety, and antitumor activity of ORIC-101 with nab-paclitaxel.

Treatment of complex limb fractures with 3D printing technology combined with personalized plates: a retrospective study of case series and literature review.

Background: In recent years, 3D printing technology has made significant strides in the medical field. With the advancement of orthopedics, there is an increasing pursuit of high surgical quality and optimal functional recovery. 3D printing enables the creation of precise physical models of fractures, and customized personalized steel plates can better realign and more comprehensively and securely fix fractures.

Surgical treatment outcomes of acetabular posterior wall and posterior column fractures using 3D printing technology and individualized custom-made metal plates: a retrospective study.

Background: Fractures involving the posterior acetabulum with its rich vascular and neural supply present challenges in trauma orthopedics. This study evaluates the effectiveness of 3D printing technology with the use of custom-made metal plates in the treatment of posterior wall and column acetabular fractures.

Methods: A retrospective analysis included 31 patients undergoing surgical fixation for posterior wall and column fractures of the acetabulum (16 in the 3D printing group, utilizing 3D printing for a 1:1 pelvic model and custom-made plates based on preoperative simulation; 15 in the traditional group, using conventional methods).

Study on the therapeutic effect of Kirschner wire tension band combined with anchor cross-stitch technique in the treatment of comminuted patellar inferopolar fractures.

Purposes: Fractures of the inferior patellar pole, unlike other patellar fractures, present challenges for traditional surgical fixation methods. This article introduces the clinical technique and outcomes of using Kirschner wire tension band combined with anchor screw cross-stitch fixation for comminuted inferior patellar pole fractures.

Methods: This retrospective case series study included 14 patients with comminuted inferior patellar pole fractures treated at our institution from September 1, 2020, to April 30, 2022.

Phase I Study of ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer Progressing on Enzalutamide.

Purpose: Increased glucocorticoid receptor (GR) signaling is a proposed compensatory mechanism of resistance to androgen receptor (AR) inhibition in metastatic castration-resistant prostate cancer (mCRPC). ORIC-101 is a potent and selective orally-bioavailable GR antagonist.

Patients And Methods: Safety, pharmacokinetic/pharmacodynamic, and antitumor activity of ORIC-101 in combination with enzalutamide were studied in patients with mCRPC progressing on enzalutamide.

3D printing technology combined with personalized plates for complex distal intra-articular fractures of the trimalleolar ankle.

This study investigated the effectiveness of 3D printing technology in combination with personalized custom-made steel plates in the treatment of complex distal intra-articular trimalleolar fractures, with the aim of providing a new approach to improve ankle joint function in patients. The 48 patients with complex distal intra-articular trimalleolar fractures included in the study were randomly divided into two groups: the personalized custom-made steel plate group (n = 24) and the conventional steel plate group (n = 24). A comparison was made between the two groups in terms of preoperative preparation time, hospitalization duration, surgical time, fracture reduction and internal fixation time, intraoperative fluoroscopy instances, surgical incision length, fracture healing time, follow-up duration, degree of fracture reduction, ankle joint functional recovery, and the occurrence of complications.

Surgical options for distal radius fractures of type C in elderly patients over 65 years old: a comparison of external fixation with Kirschner wires and volar locking plate.

Background: ue to the lack of consensus on the optimal surgical treatment for distal radius fractures (DRF) in elderly patients over 65 years old, the purpose of this study was to compare the efficacy of external fixation (EF) with Kirschner wires and volar locking plate (VLP) in the treatment of DRF through a retrospective cohort study. We hypothesized that there would be no significant difference in overall complications and functional recovery between the two methods.

Methods: We retrospectively analyzed 62 patients over 65 years old who underwent surgical treatment for C-type DRF between 2019 and 2022.

AC0010, an Irreversible EGFR Inhibitor Selectively Targeting Mutated EGFR and Overcoming T790M-Induced Resistance in Animal Models and Lung Cancer Patients.

AC0010 is a pyrrolopyrimidine-based irreversible EGFR inhibitor, structurally distinct from previously reported pyrimidine-based irreversible EGFR inhibitors, such as osimertinib and rociletinib. AC0010 selectively inhibits EGFR-active and T790M mutations with up to 298-fold increase in potency compared with wild-type EGFR. In a xenograft model, oral administration of AC0010 at a daily dose of 500 mg/kg resulted in complete remission of tumors with EGFR-active and T790M mutations for over 143 days with no weight loss.

Preparative two-dimensional liquid chromatography/mass spectrometry for the purification of complex pharmaceutical samples.

A new preparative two-dimensional liquid chromatography/mass spectrometry system (2D LC-LC/MS) has been designed and implemented to enhance capability and resolving power for the separation and purification of pharmaceutical samples. The system was constructed by modifications of a conventional preparative LC/MS instrument with the addition of a set of switching valves and a sample loop, as well as interfacing a custom software program with MassLynx. The system integrates two chromatographic separations from the first and second dimensions into a single automated run to perform the purification of a target compound from a complex mixture without intermediate steps of sample preparation.

Two-dimensional supercritical fluid chromatography/mass spectrometry for the enantiomeric analysis and purification of pharmaceutical samples.

A new analytical two-dimensional supercritical fluid chromatography/mass spectrometry system (2D SFC/SFC/MS) has been designed and implemented to enhance the efficiency and quality of analytical support in drug discovery. The system consists of a Berger analytical SFC pump and a modifier pump, a Waters ZQ 2000 mass spectrometer, a set of switching valves, and a custom software program. The system integrates achiral and chiral separations into a single run to perform enantiomeric analysis and separation of a racemic compound from a complex mixture without prior clean up.

[Observation on short and long-term effects of cervical spondylotic radiculopathy treated with abdominal acupuncture plus Long's bone-setting manipulation].

Objective: To compare the short and long-term therapeutic effects on cervical spondylotic radiculopathy (CSR) treated with simple Long's bone-setting manipulation, abdominal acupuncture and abdominal acupuncture plus Long's bone-setting manipulation.

Methods: One hundred and eighty cases of CSR were randomly allocated into abdominal acupuncture plus bone-setting group (combined therapy group), bone-setting group and abdominal acupuncture group, 60 cases in each group. In combined therapy group, the abdominal acupuncture and Long's bone-setting were applied in combination.

Design and synthesis of pyrimidinone and pyrimidinedione inhibitors of dipeptidyl peptidase IV.

The discovery of two classes of heterocyclic dipeptidyl peptidase IV (DPP-4) inhibitors, pyrimidinones and pyrimidinediones, is described. After a single oral dose, these potent, selective, and noncovalent inhibitors provide sustained reduction of plasma DPP-4 activity and lowering of blood glucose in animal models of diabetes. Compounds 13a, 27b, and 27j were selected for development.

A high throughput metabolic stability screening workflow with automated assessment of data quality in pharmaceutical industry.

One of the most commonly performed in vitro ADME assays during the lead generation and lead optimization stage of drug discovery is metabolic stability evaluation. Metabolic stability is typically assessed in liver microsomes, which contain Phase I metabolizing enzymes, mainly cytochrome P450 enzymes (CYPs). The amount of parent drug metabolized by these CYPs is determined by LC/MS/MS.

Parallel SFC/MS-MUX screening to assess enantiomeric purity.

Enantiomeric excess (ee) was evaluated for two internally synthesized compound libraries using a high-throughput automated, intelligent four-channel parallel supercritical fluid chromatography/mass spectrometry system equipped with a multiplexed ion source interface (SFC/MS-MUX). The two libraries contained compounds spanning a wide range of enantiomeric ratios with structurally diverse chemical scaffolds and stereogenic centers. The system analyzed each sample simultaneously against four chiral columns using up to six organic modifiers.

Structure-based design and synthesis of benzimidazole derivatives as dipeptidyl peptidase IV inhibitors.

A novel series of non-covalent, benzimidazole-based inhibitors of DPP-4 has been developed from a small fragment hit using structure-based drug design. A highly versatile synthetic route was created for the development of SAR, which led to the discovery of potent and selective inhibitors with excellent pharmaceutical properties.

Parallel supercritical fluid chromatography/mass spectrometry system for high-throughput enantioselective optimization and separation.

An automated parallel four-column supercritical fluid chromatography (SFC)/MS system to perform high-throughput enantioselective chromatographic method development and optimization is described in this paper. The initial screening was performed in parallel on four chiral SFC columns over several buffer conditions. Optimization of the separation of enantiomers was achieved on a single chiral column.

Discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV.

Alogliptin is a potent, selective inhibitor of the serine protease dipeptidyl peptidase IV (DPP-4). Herein, we describe the structure-based design and optimization of alogliptin and related quinazolinone-based DPP-4 inhibitors. Following an oral dose, these noncovalent inhibitors provide sustained reduction of plasma DPP-4 activity and a lowering of blood glucose in animal models of diabetes.

Cell-based assay for screening 11beta-hydroxysteroid dehydrogenase inhibitors using liquid chromatography/tandem mass spectrometry detection.

Cortisol is an important glucocorticoid that regulates many physiological pathways by activating various intracellular receptors. The type 1 isozyme of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) functions in vivo predominantly as a reductase by converting cortisone into cortisol. A high-throughput liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed to screen for inhibitors of 11beta-HSD1 by monitoring cortisol and cortisone simultaneously.

Automated high throughput ADME assays for metabolic stability and cytochrome P450 inhibition profiling of combinatorial libraries.

Early determinations of pharmaceutical properties can serve as predictors of a compound's likely development success. Our laboratory has implemented high throughput in vitro absorption, distribution, metabolism and excretion (ADME) assays which address absorption, metabolism, and physico-chemical properties in an effort to identify potential development liabilities early, thereby minimizing discovery to market attrition. In response to the throughput demands of parallel synthesis, we have incorporated a SAGIAN core robotics system for the determination of both metabolic stability in human liver microsomes (HLMs) and cytochrome P450 (CYP450) inhibition.

High-throughput mass-directed parallel purification incorporating a multiplexed single quadrupole mass spectrometer.

We report on the development of a parallel HPLC/MS purification system incorporating an indexed (i.e., multiplexed) ion source.

Application of parallel liquid chromatography/mass spectrometry for high throughput microsomal stability screening of compound libraries.

Solution-phase and solid-phase parallel synthesis and high throughput screening have enabled biologically active and selective compounds to be identified at an unprecedented rate. The challenge has been to convert these hits into viable development candidates. To accelerate the conversion of these hits into lead development candidates, early assessment of the physicochemical and pharmacological properties of these compounds is being made.