Integrated bioinformatic analysis of the molecular mechanisms between type 2 diabetes mellitus and osteoarthritis.

Type 2 diabetes mellitus (T2DM) is a metabolic syndrome that has been identified as an independent risk factor for osteoarthritis (OA) and may even trigger and exacerbate the progression of OA. However, the relationship between T2DM and OA is complex and has not yet been fully clarified by current research. In this study, we analyzed the potential mechanism of action between T2DM and OA by bioinformatics. Transcriptome sequencing data of T2DM (GSE25724) and OA (GSE55235) were downloaded from the gene expression omnibus. Differential expression analysis was performed for different subgroups to obtain differentially expressed genes. The protein-protein interaction network was constructed using overlapping genes and screened for hub targets. Then the enrichment analysis was performed separately for overlapping and hub targets. The GeneMANIA is used to predict functionally similar genes of hub genes. Differential expression analyses revealed that 184 genes are involved in both diseases together. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment results showed that the overlapping genes were mainly involved in the advanced glycation end products-receptor of advanced glycation end products signaling pathway, the NF-kappa B signaling pathway, the mitogen-activated protein kinases signaling pathway, and the interleukin-17 signaling pathway in diabetic complications. The functions of genes similar to the hub genes are focused on cell chemotaxis, positive regulation of cell migration, positive regulation of RNA polymerase II transcription, regulation of leukocyte migration, epithelial cell proliferation, and integrated stress response signaling. The transcription factor Jun and C-X-C motif chemokine 8 may play an important role in the inflammatory response caused by advanced glycation end products. This study improves our understanding of T2DM complicating OA and helps to stimulate more effective treatments.

Arthroscopic medial patellofemoral ligament reconstruction with polyethylene suture combined with medial retinaculum plication for the treatment of acute patellar dislocation in young and middle-aged patients with a follow-up of at least 2 years.

PURPOSE: The purpose of this study was to propose a surgical technique for arthroscopic medial patellofemoral ligament (MPFL) reconstruction with polyethylene suture combined with medial retinaculum plication and to evaluate the efficacy of this surgical technique in the treatment of acute patellar dislocation. METHODS: Clinical data of patients with acute patellar dislocations treated with arthroscopic MPFL reconstruction with polyethylene tape (FiberTape) combined with medial support band compression were analyzed retrospectively from January 2018 to January 2021. The mean age of the patients was 25.15 ± 4.66 years; the mean follow-up time was 27.5 (24-36) months. Clinical evaluation consisted of apprehension test results, patellar extrapolation test results, Lysholm score, Kujala score, and IKDC score, the Patellar lateral shift distance and patellar tilt angle (PTA) measured by CT scan. RESULTS: All patients had no recurrent patellar dislocation or subluxation after surgery, and the apprehension test was negative. In all patients, the Kujala score (36.0 ± 9.9 vs. 98.2 ± 3.1), the IKDC score (48.6 ± 7.0 vs. 90.6 ± 4.4) and the Lysholm score (32.8 ± 10.4 vs. 96.7 ± 3.1) had improved at the 24-month follow up (P < 0.05). In addition, PTA was significantly lower at the 12-month follow-up and 24-giving-month follow-up compared to the preoperative period (P < 0.05, Table 2). The patellar lateral shift distance decreased from 14.94 ± 6.11 mm preoperatively to 3.00 ± 1.40 mm (12-month follow up) and 3.26 ± 1.37 mm (24-month follow up), respectively. CONCLUSION: Arthroscopic MPFL reconstruction with polyethylene suture combined with medial retinaculum plication is a safe and reliable surgical technique for the treatment of acute patellar dislocation in young and middle-aged patients. LEVEL OF EVIDENCE: Level III, Therapeutic Study.

[Effectiveness of proximal femoral nail antirotation assisted by mesh locator for intertrochanteric fracture in the elderly].

OBJECTIVE: To explore the effectiveness of proximal femoral nail antirotation (PFNA) assisted by mesh locator in treatment of intertrochanteric fracture in the elderly. METHODS: Ninety-four elderly patients with intertrochanteric fractures admitted between August 2014 and July 2017 were selected as the study subjects. They were randomly divided into trial group (48 cases) and control group (46 cases). In trial group, PFNA was implanted assisted by mesh locator after closed reduction; while in control group, PFNA was implanted by conventional method. There was no significant difference between the two groups in terms of gender, age, cause of injury, time from injury to admission, fracture side and classification, and medical complications ( P>0.05). The operation time, intraoperative blood loss, fluoroscopy times, hospital stay, incision length, and complications were recorded. Visual analogue scale (VAS) was used to evaluate the degree of pain at 3 days after operation, and Harris score was used to evaluate hip function before operation and at 3, 6, and 9 months after operation. RESULTS: Compared with control group, the operation time and incision length of trial group shortened, the blood loss and fluoroscopy times reduced, the pain after operation alleviated obviously; the differences between the two groups were significant ( P<0.05). There was no significant difference in hospital stay between the two groups ( P>0.05). The patients in both groups were followed up 9-12 months, with an average of 10.6 months. X-ray films showed that the fractures healed in both groups, and the healing time in control group was (11.2±3.2) weeks, while that in trial group was (11.6±2.9) weeks, showing no significant difference between the two groups ( t=1.262, P=0.120). There was no significant difference in Harris score between the two groups before operation and at 3, 6, and 9 months after operation ( P>0.05). There was 1 case of incision infection, 2 cases of coxa vara, and 1 case of pressure ulcer in trial group, and the incidence of complications was 8.3%. There was 1 case of coxa vara, 2 cases of pressure ulcer, and 1 case of internal fixation loss in control group, and the incidence of complications was 8.7%. There was no significant difference in the incidence of complications between the two groups (χ 2=0.783, P=0.112). CONCLUSION: It is feasible to implant PFNA assisted by mesh locator in treatment of intertrochanteric fracture in the elderly. Compared with the traditional operation, it can shorten the operation time, shorten the incision, and relieve the pain after operation.

Quantitative determination of unbound levofloxacin by simultaneous microdialysis in rat pancreas after intravenous and oral doses.

OBJECTIVE: We compared the pharmacokinetic profile of unbound levofloxacin in rat pancreas after an oral dose with that after an intravenous dose to determine if oral administration of levofloxacin could potentially be used. METHOD: Levofloxacin was administered either intravenously or orally into male Sprague-Dawley rats at the concentration of 42 mg/kg per day, mimicking the human dose of 400 mg/day. The concentrations of levofloxacin in extracellular fluid (ECF) of rat pancreatic tissues were determined using microdialysis coupled with high-performance liquid chromatography (HPLC). Levofloxacin was equally distributed into ECF of rat pancreatic tissues with either intravenous route (AUCpancreas /AUCblood , 0.97 ± 0.02) or oral route (AUCpancreas /AUCblood , 0.96 ± 0.03). KEY FINDINGS: The penetration rates (PR) of pancreas-to-blood on the same target site between the two routes were the same. The intravenous antibiotic AUC/MIC ratios of common Gram-positive pancreatic bacteria ranged from 83.43 to 667.44; meanwhile, the ratio of common Gram-negative pancreatic bacteria ranged from 41.71 to 2669.74. The oral antibiotic AUC/MIC ratios for common gram-positive and Gram-negative pancreatic bacteria were from 78.54 to 628.31, and 39.27 to 2513.22, respectively (P > 0.05). CONCLUSIONS: Intravenous administration had similar penetration efficacy to oral administration at an equivalent dose. Furthermore, levofloxacin had a good penetration through the blood-pancreas barrier.

Comparison of the cable pin system with conventional open surgery for transverse patella fractures.

BACKGROUND: The cable pin system is an effective device for fixation of transverse patella fractures. However, whether this device provides superior results using a minimally invasive technique instead of conventional open surgery using the K wire tension band method is unclear. QUESTIONS/PURPOSES: We asked whether a minimally invasive technique would be associated with (1) increased operative time; (2) reduced postoperative pain; (3) faster recovery of ROM; (4) higher knee scores; and (5) reduced complications. METHODS: Forty patients with displaced transverse fractures of the patella participated in this prospective, randomized, controlled trial. Twenty of these patients underwent a minimally invasive technique and the others had conventional open surgery using K wires. Some data for six of the 20 patients who underwent the minimally invasive technique were published in an earlier prospective, observational trial. At postoperative intervals of 1, 3, 6, 12, and 24 months, pain was measured by VAS scores, active flexion and extension of the knee were measured in degrees by goniometry, and knee function was evaluated using the Böstman clinical grading scale. RESULTS: Operative time was longer in the minimally invasive surgery group (54.3 ± 9.8 minutes versus 48.5 ± 6.1 minutes). Pain scores were better (lower) in the minimally invasive surgery group at 1 and 3 months but not at 6 months. Early flexion, ultimate flexion, and knee scores from 3 to 24 months, likewise, were better in the minimally invasive surgery group. Complications mostly related to symptomatic hardware were less common in the minimally invasive surgery group. CONCLUSIONS: The minimally invasive technique is superior to conventional open surgery using K wires in terms of less early postoperative pain, better mobility angles of the injured knee, higher functional score of the injured knee, and decreased incidence of complications. LEVEL OF EVIDENCE: Level I, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Long-term outcomes of one-stage anterior debridement, bone grafting, and internal fixation for the treatment of lower cervical tuberculosis with kyphosis.

BACKGROUND: Patients with spinal deformities and nerve compression due to spinal tuberculosis often require surgical intervention. The objective of this study was to assess the long-term therapeutic effectiveness of one-stage anterior debridement, bone grafting, and internal fixation for lower cervical tuberculosis with kyphosis. METHODS: Twenty-one patients with lower cervical tuberculosis and cervical kyphosis received one-stage anterior debridement, autologous iliac bone grafting, and internal plate fixation. Patients were followed-up postoperatively for at least 5 years. Outcome measures included neck pain using Visual Analogue Scale (VAS) scores, Frankel classification of spinal cord injury, and Cobb angle of cervical kyphosis. RESULTS: Eighteen patients had lesions in 2 vertebrae and 3 had lesions in 3 vertebrae. Cervical tuberculosis was cured in all patients. The mean preoperative VAS score for neck pain was 8 (range: 6-10), whereas the mean best postoperative VAS score was 0.6 (range: 0-3). Mean final VAS score was significantly higher than the best VAS score (2.14 vs. 0.62). Of the 13 patients with symptoms of spinal cord compression, 9 improved by 1 grade and 4 improved by 2 grades according to Frankel classification at final follow-up. The mean preoperative Cobb angle of cervical kyphosis was 29° (range: 15°-50°), whereas the mean postoperative Cobb angle at final follow-up was -1.8° (range: 2-7°). CONCLUSIONS: One-stage anterior debridement, bone grafting, and internal fixation can effectively remove lesions, decompress the nerve, reduce pain, and correct kyphosis in patients with cervical tuberculosis and associated kyphosis. Long-term postoperative outcomes were satisfactory.

[Pharmacokinetics of scopolamine hydrobromide oral disintegrative microencapsule tablets in Beagle dogs determined with LC-MS/MS].

The study aims to elucidate the characteristics of pharmacokinetics of scopolamine hydrobromide oral disintegrative microencapsule tablets in healthy Beagle dogs. Chromatographic separation was performed on a C18 column (100 mm x 3.0 mm, 3.5 microm) with methanol - 2 mmol x L(-1) ammonium formate (25 : 75) as the mobile phase. A trip-quadrupole tandem mass spectrum with the electrospray ionization (ESI) source was applied and positive ion multiple reaction monitoring mode was operated. Six Beagle dogs were randomly devided into two groups. They received oral single dose of scopolamine hydrobromide oral disintegrative microencapsule tablets 0.6 mg (test tablet) or scopolamine hydrobromide normal tablets (reference tablet). Plasma samples were collected at designed time. Plasma concentration of scopolamine hydrobromide was determined by LC-MS/MS and pharmacokinetic parameters were calculated. The pharmacokinetic parameters of test tablet vs reference tablet were as follows: C(max): (8.16 +/- 0.67) ng x mL(-1) vs (3.54 +/- 0.64) ng x mL(-1); t1/2: (2.83 +/- 0.45) h vs (3.85 +/- 0.82) h; t(max): (1.25 +/- 0.27) h vs (0.42 +/- 0.09) h; AUC(0-12h): (25.06 +/- 3.75) h x ng x mL(-1) vs (9.59 +/- 1.02) h x ng x mL(-1); AUC(0-infinity): (26.30 +/- 3.92) h x ng x mL(-1) vs (10.80 +/- 1.45) h x ng x mL(-1); MRT(0-12h): (3.38 +/- 0.34) h vs (3.86 +/- 0.26) h; MRT(0-infinity): (3.98 +/- 0.63) h vs (5.37 +/- 1.00) h. The absorption rate and AUC of test tablet is different from that of reference tablet. The bioavailability of test tablet is better than those of reference tablet.