Roles of human periodontal ligament stem cells in osteogenesis and inflammation in periodontitis models: Effect of 1α,25-dihydroxyvitamin D3.

Periodontitis is a chronic inflammatory disease caused by Porphyromonas gingivalis and other bacteria, and human periodontal ligament stem cells (hPDLSCs) are a promising candidate for the treatment of periodontal supporting tissue defects. This study aimed to investigate the effect of 1α,25-dihydroxyvitamin D3 [1,25(OH)2VitD3] on osteogenic differentiation of hPDLSCs in an in vitro periodontitis model and whether it can improve inflammatory status. hPDLSCs were in vitro isolated and identified. After treatment with 1,25(OH)2VitD3 and ultrapure pure Porphyromonas gingivalis lipopolysaccharide (LPS-G), the viability of hPDLSCs was detected using Cell Counting Kit-8, the expressions of osteogenic markers and inflammatory genes using Western blotting and quantitative reverse transcription PCR (qRT-PCR), the levels of inflammatory factors in cells using enzyme linked immunosorbent assay (ELISA), and the fluorescence signal intensity of osteoblastic markers and inflammatory genes in cells using immunofluorescence assay. It was found that 1,25(OH)2VitD3 reversed the inhibition of hPDLSCs proliferation by LPS-G; LPS-G exhibited inhibitory effect on ALP, Runx2, and OPN expressions, and such inhibitory effect was significantly weakened when co-acting with 1,25(OH)2VitD3. Meanwhile, LPS-G upregulated the expressions of inflammatory genes IL-1ß and Casp1, whereas 1,25(OH)2VitD3 antagonized such an effect and improved the inflammatory status. In conclusion, 1,25(OH)2VitD3 can reverse the inhibitory effect of LPS-G on hPDLSCs proliferation and osteogenic differentiation and suppress LPS-G-induced upregulation of inflammatory gene expressions.

Safety, tolerability, and pharmacokinetics of fluoropezil (DC20), a novel acetylcholinesterase inhibitor: A phase I study in healthy young and elderly Chinese subjects.

The present study evaluated the safety, tolerability, and pharmacokinetics of fluoropezil (DC20), a novel acetylcholinesterase inhibitor under development for the treatment of Alzheimer's disease (AD) in otherwise healthy young and elderly Chinese subjects. The study of young subjects included the multiple ascending dose (MAD) arm (2 and 6 mg, N = 24) and the food effect arm (4 mg, N = 12) and was followed by the study of elderly subjects who were given (2 and 4 mg, N = 11). The noncompartmental analysis method was used to determine the pharmacokinetic parameters. The pharmacokinetics of fed versus fasted dose administration in the same subjects was assessed by 90% confidence interval. In the MAD arm, the accumulation ratios of DC20 in vivo were 2.29 and 2.15, respectively. In the food effect arm, compared with fasting administration, an area under the concentration-time curve from zero to t after a standard and high-fat diet orally administered slightly increased by about 19% and 29%, and the time to maximum concentration (Tmax ) was delayed by around 1 h. For elderly study subjects, Tmax was 1.5 and 1.25 h, and terminal half-life (t1/2 ) was 77.1 and 74.2 h, respectively. There were no serious adverse events (AEs), whereas gastrointestinal reactions were the most common AEs associated with the study drug. We predicted the safety risks of DC20 in the clinical treatment of AD, which were well-tolerated by the healthy young and elderly subjects. The elimination of DC20 from the body was slower in elderly subjects than in young subjects. This study was approved by the Center for Drug Evaluation, National Medical Products Administration (CTR20181428, CTR20190664, CTR20191878, and CTR20192724).

Robot guided balloon tibial osteoplasty with screw fixation for the treatment of Schatzker II and III tibial plateau fractures / 中华骨科杂志

Objective:To explore the clinical efficacy of robot guided balloon tibial osteoplasty for the treatment of Schatzker II and III tibial plateau fractures.Methods:A retrospective analysis was conducted on the data of 59 patients admitted from January 2017 to December 2022. According to the surgical method, they were divided into two groups: robot guided percutaneous balloon tibial osteoplasty with "Jail" screw fixation group (study group) and open reduction and internal fixation group (control group). There were 28 cases in the study group, including 13 males and 15 females, with an average age of 44.21±9.70 years. In the study group, 8 cases were diagnosed of Schatzker II and 20 cases of Schatzker III. There were 31 cases in the control group, including 16 males and 15 females, with an average age 47.94±13.73 years. In the control group 7 cases were diagnosed of Schatzker II and 24 cases of Schatzker III. Between the two groups, demographics, surgical challenges and outcomes were all compared, including age, fracture classification, fracture collapse volume, surgical time, intraoperative bone graft volume, incision length, postoperative drainage volume, length of stay, fracture reduction quality (proportion of collapse area reduction volume evaluated by postoperative CT, Rasmussen radiology score), knee joint hospital for special surgery (HSS) score at 6 months after surgery, pain visual analogue scale (VAS) scores at before and 3 days after surgery and the final follow-up, complications.Results:All the patients were followed up for 116.92±6.08 months. The surgical time was 88.50±21.32 min in the study group, and 65.16±18.10 min in the control group with significant difference ( t=4.55, P<0.001). Between the study group and the control group, the intraoperative bone graft volume (3.04±1.15 cm 3vs. 5.87±2.03 cm 3), incision length (3.34±1.02 cm vs. 17.65±2.33 cm), postoperative drainage volume (13.04±19.45 ml vs. 85.16±41.54 ml), and length of hospital stay (11.64±3.07 d vs. 18.77±4.78 d) were all found to be significantly differently ( t=-6.69, P<0.001; t=-31.02, P<0.001; t=-8.67, P<0.001; t=-7.06, P<0.001). After 6 months of surgery, Rasmussen's radiological score was 17.32 ± 1.06 in the study group and 17.58 ± 0.85 in the control group with no significant difference ( t=-1.04, P=0.150). After 6 months of surgery, the HSS score in the study group was 93.75±2.22, and 92.71±2.19 in the control group with significant difference ( t=1.81, P=0.038). The VAS score between the study and control group was 7.04±0.92 vs. 7.00±0.97 before the surgery, 2.71±0.85 vs. 4.74±0.93 three days after surgery, and 0.21±0.49 vs. 0.26±0.51 at the final follow-up with significant pain relief at either three days or the final follow up within either group ( F=1884.53, P<0.001; F=55.98, P<0.001). Significant difference between the two groups was found at three days after the surgery ( t=-10.28, P<0.001), while no significant difference was found before surgery or at the final follow-up ( P>0.05). The wounds in the study group healed well, while in the control group, 4 cases had poor wound healing. One case in the study group had intraoperative balloon rupture and contrast agent leakage, while two cases had bone graft material leakage. There were no intraoperative complications in the open group. Conclusion:Robot guided balloon tibial osteoplasty for Schatzker II and III tibial plateau fractures had achieved satisfactory reduction, minimal bleeding, minimal trauma, short hospital stay, good knee joint function recovery, and satisfactory clinical results. However, attention should be paid to the issue of contrast agent leakage caused by balloon rupture.

Accuracy of infra-acetabular screw implantation assisted by a 3D-printed personalized screw guide in vitro / 中华创伤骨科杂志

Objective:To investigate the accuracy of infra-acetabular screw implantation assisted by a 3D-printed personalized screw guide in vitro. Methods:The imaging data were collected of the 10 patients with acetabular fracture involving the anterior column who had been treated at Department of Orthopaedics, The Fourth Hospital of Wuhan from June 2015 to October 2021. There were 8 males and 2 females, with an average age of (42.6±2.1) years. According to the Letournel-Judet classification, there were 2 anterior column fractures, 4 anterior column + posterior semi-transverse fractures, 3 double column fractures, and 1 T-shaped fracture. The thin-slice CT scan data of the patients’ pelves were imported into the E3D software to generate digital 3D fracture models in which fracture reduction and post-reduction were simulated and personalized screw guides for infra-acetabular screw implantation were generated. After the above models were printed by a 3D printer, the fracture models were reduced in vitro and the infra-acetabular screws were implanted assisted by the personalized guide on the affected and healthy acetabulum models. After operation, the printed models were scanned by CT again, and the CT data were imported into the E3D software again to generate the postoperative digital 3D models. The position relationships were observed between the screws and the cortex around the corridor on the postoperative CT scan images. The consistency of the position parameters was compared between pre- and post-operation for each screw in the digital models. Results:Ten personalized screw guides were generalized respectively for the affected and healthy sides of the 10 patients in this group. Anatomical reduction was achieved in vitro in all the 3D printed fracture models. A total of 20 infra-acetabular screws were implanted with the assistance by the screw guide. According to the Andrew's CT grading for pedicle screw positions, 19 infra-acetabular screws were rated as grade Ⅰ and 1 was rated as grade Ⅱ. The linear distance from the midpoint of the pubic symphysis to the point of insertion, and the angles between the axis of the screw and the horizontal, sagittal and coronal planes on the health side before operation were respectively (60.65±5.55) mm, 23.96°±5.59°),2.88 °±1.25°, and 65.06°±5.48°, showing insignificant differences from the postoperative values [(60.91±5.73) mm, 24.00°±6.15°, 3.20°±1.13°, and 65.74°±5.57°] ( P>0.05); the above screw position parameters on the affected side before operation were respectively (60.76±4.41) mm, 24.77°±2.97°, 3.06° (2.66°, 3.68°), and 63.70° (62.70°, 65.60°), showing insignificant differences from the postoperative values [(60.71±4.56) mm, 24.67°±2.73°, 3.04° (2.64°, 3.51°), and 64.40°(63.20°, 65.90°)] ( P>0.05). Conclusion:In the models in vitro, implantation of infra-acetabular screws assisted by a 3D printed personalized screw guide can be highly accurate, owing to insignificant differences in all the position parameters between the simulated operations and the operations in vitro.

LC-MS/MS assay of fluoropezil and its two major metabolites in human plasma: an application to pharmacokinetic studies.

Background: LC-MS/MS methods were developed for pharmacokinetic analysis and verified to measure fluoropezil, a new AchE inhibitor for Alzheimer's disease treatment, and its two primary metabolites (N-debenzyl fluoride fluoropezil [M1] and N-oxidized fluoropezil [M11]) in human plasma. Methods & results: Analytes were extracted from 50 µl plasma using protein precipitation and separated by HPLC using a bridged ethyl hybrid column and gradient elution procedure. Analytical detection was performed with a triple quadrupole mass spectrometer and electrospray ionization source in multiple reaction monitoring mode. The LC-MS/MS method was fully validated. The quantification linear ranges were 0.100-50.0 ng/ml (fluoropezil), 0.0500-25.0 ng/ml (M1) and 0.0500-25.0 ng/ml (M11). Conclusion: A sensitive, reliable LC-MS/MS method was established and used successfully to explore the pharmacokinetics of fluoropezil.

Value of aortic root CTA assessment in aortic valve surgery / 中国胸心血管外科临床杂志

@#Objective    To evaluate the data of preoperative aortic root CT angiography (CTA), compare it with two-dimensional transthoracic echocardiography and investigate the correlation of the two measurements with the actual intraoperative measurement data. Methods    Clinical data of 53 patients with aortic valve diseases who underwent aortic valve repair in our hospital from January 2018 to August 2020 were retrospectively analyzed, including 38 males and 15 females with an average age of 42.9±18.3 years ranging from 10 to 77 years. Preoperative two-dimensional transthoracic echocardiography (TTE) and aortic root CTA measurements were collected, including aortic valve annulus (AVA), aortic sinus (Sinus) and sino-tubular junction (STJ). In comparison with the intraoperative measurements during the aortic valve repair surgery, the consistency analysis was performed. Results    Both the preoperative echocardiography AVA measurements and the CT AVA measurements were positively correlated with the intraoperative AVA measurements (P<0.001). Compared with the echocardiography AVA data [correlation coefficient (ρ)=0.74, mean squared error (MSE)=12.78], the CT AVA data were more accurate and consistent with the intraoperative AVA measurements (ρ=0.95, MSE=2.72). CT AVA data had a higher correlation coefficient with the intraoperative measurements, compared to that of  the echocardiography AVA data (P<0.001). Conclusion    In comparison with two-dimensional transthoracic echocardiography, preoperative morphological evaluation of aortic root CTA is more consistent with the actual intraoperative measurements during aortic valve repair surgery.

Comparison of Gamma 3 U-blade system and Gamma 3 nails in treatment of elderly patients with osteoporotic unstable femoral intertrochanteric fracture / 中华创伤骨科杂志

Objective:To compare the short-term therapeutic effects of Gamma 3 U-Blade system and Gamma 3 nails in the treatment of elderly patients with osteoporotic unstable intertrochanteric fracture.Methods:The data of 70 elderly patients with osteoporotic unstable intertrochanteric fracture were retrospectively analyzed who had been admitted to the Department of Orthopedics, Wuhan Fourth Hospital from June 2018 to December 2020. They were divided into 2 groups according to their treatments. In the U-Blade group of 35 cases subjected to fixation with Gamma 3 U-Blade system, there were 14 males and 21 females with an age of (77.7 ± 4.8) years; in the Gamma 3 nail group of 35 cases subjected to fixation with Gamma 3 nails, there were 14 males and 21 females with an age of (79.3 ± 5.2) years. The 2 groups were compared in terms of operation time, intraoperative blood loss, apex distance, fracture union time, postoperative complications, timed up and go (TUG) at postoperative 2 weeks, 3 months and 6 months, and hip function at postoperative 9 months.Results:There was no statistically significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). There was no significant difference either in operation time, intraoperative blood loss or apex distance between the 2 groups ( P>0.05). The fracture union time [(12.0 ± 0.2) weeks] and Harris hip score at postoperative 9 months [90 (90, 91)] in the U-Blade group were insignificantly different from those in the Gamma 3 nail group [(12.0 ± 0.3) weeks and 91 (89, 91)] ( P>0.05). The rate of implant-related complications in the U-Blade group [0% (0/35)] was significantly lower than that in the Gamma 3 nail group [17.1% (6/35)] and the TUGs at postoperative 2 weeks and 3 months [(80.2 ± 3.6) s and 45 (43, 49) s] in the former were significantly shorter than those in the latter [(89.3 ± 4.2) s and 56 (54, 59) s] ( P<0.05). Conclusion:In the treatment of elderly patients with osteoporotic unstable intertrochanteric fracture, compared with traditional Gamma 3 nails, Gamma 3 U-Blade system can reduce implant-related complications and facilitate early recovery of walking ability.

Analysis of risk factors and construction of a prediction model for mild cognitive impairment in elderly inpatients in sub-plateau areas / 中华老年医学杂志

Objective:To investigate the prevalence of mild cognitive impairment(MCI)in elderly inpatients in high altitude areas, analyze the influencing factors, and then construct a risk factor model.Methods:A cross-sectional random sampling method was used to conduct a questionnaire survey among elderly patients over 65 years old hospitalized at Qinghai Provincial People's Hospital from October 2018 to February 2019.The survey contents included demographic data, lifestyles, physical activities and cognitive function.The occurrence of MCI was analyzed with descriptive epidemiological measures, a predictive model of influencing factors was established using Logistic regression analysis, and influencing factors were ranked.Results:There were a total of 1412 elderly people aged 65 and above, with 760 males, accounting for 53.8%.The ages of respondents ranged between 65-82 years, with an average age of(72.8±5.8)years.Of the subjects, 600 had MCI, with a prevalence of 42.4%.Male( OR=1.318, P=0.02), junior high school education or above( OR=0.521, P<0.001), bedriddenness( OR=2.658, P=0.002), lifestyle( OR=0.702, P=0.011), abnormal defecation( OR=1.625, P=0.005)and frailty( OR=1.536, P=0.002)were included into the predictive model of influencing factors.The area under the ROC curve in this study was 0.676(95% CI: 0.648-0.704), with sensitivity=0.553, specificity=0.741, and Youden index=0.274.When ordered by importance, the independent risk factors were frailty, male, abnormal defecation, bedriddenness, lifestyle, and education level. Conclusions:Male, frailty, abnormal defecation and long-term bedriddenness are risk factors for cognitive impairment in elderly people, whereas living with a partner and education above junior high school are protective factors.

Analysis of cognitive dysfunction and its influencing factors in elderly inpatients in Qinghai / 中华老年医学杂志

Objective:To evaluate the cognitive function of elderly inpatients in Qinghai and analyze the influencing factors in this prospective study.Methods:A total of 1077 elderly inpatients were enrolled for general information investigation, including the Mini Nutritional Assessment-Short form(MNA-SF), Geriatric Depression Scale 15(GDS-15), FRAIL Scale, activities of daily living(ADL), instrumental ability of daily living(IADL)and the Mini-Mental State Examination(MMSE).Results:The 1077 elderly inpatients being subjected in this study, included 470 in the cognitive impairment(CI)group and 607 in the normal group.The prevalence of CI in hospitalized elderly patients was 43.64%(470/1077). The results of univariate analysis showed that as compared with the normal group, the proportion of cognitive impairment was higher in female, elder patients, and boiling tea-drinker, otherwise the proportion of CI was lower in patients living with the spouse, normal sleep, often eating beef and mutton( P<0.01 or P<0.05); FRAIL Scale, ADL total score, and IADL total score were higher in the normal group than in the CI group( P<0.01); the elderly depression score and frailty score were higher in the CI group than in the normal group( P<0.01). The results of logistic regression analysis showed that the risk of CI was higher in female and people frequently drinking boiling tea than in male and people not frequently drinking boiling tea( OR=0.740, 1.211, both P<0.05), and that frequent consumption of beef and mutton, and reasonable levels of nutrition, ADL, and IADL were protective factors for CI in elderly hospitalized patients( OR=0.780, 0.938, 0.956, 0.895, all P<0.05). Conclusions:The incidence of cognitive impairment in hospitalized elderly patients in Qinghai is relatively high.Female and often drinking boiling tea may increase the risk of cognitive impairment.Regularly eating beef and mutton, reasonable levels of nutrition, maintaining good daily life ability can delay cognitive impairment.

Research progress on medical interprofessional education / 中华医学教育探索杂志

Interprofessional education (IPE) is of great importance to the cultivation of medical students, which can improve their ability of team cooperation in medical work in the future and can also improve the treatment experience of patients. This paper focuses on the general situation of the development of medical IPE and organizational forms, capacity building framework, curriculum development, influencing factors, teaching evaluation, existing problems, and enlightenments on the development of medical IPE in China.