Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

OBJECTIVE To prepare a self-microemulsifying drug delivery system(SMEDDS) for the oral administration of nebivolol hydrochloride(NBH) and to conduct in vitro evaluation. METHODS The solubility of NBH was determined using various oil phases, surfactants, and co-surfactants. The composition of the blank self-microemulsifying formulation was determined using pseudo-ternary phase diagrams. A centralcomposite design-response surface method was employed to screen and optimize the formulation variables, and an excess amount of NBH raw material was incorporated to determine the drug loading capacity. RESULTS The optimized composition of the NBH-SMEDDS formulation consisted of medium-chain glycerides, capryl caproyl macrogol glycerides, and 2-(2-ethoxyethoxy) ethyl acetate at a ratio of 20∶48∶32, with a drug loading capacity of 20.05 mg. The particle size, self-emulsification time, and particle size distribution range of the formulation were in agreement with the predicted values. Dissolution testing demonstrated that the overall dissolution trend of NBH-SMEDDS in the medium was higher than that of NBH powder and NBH ordinary tablet. The stability of NBH-SMEDDS was found to be satisfactory under accelerated conditions for 1, 2, and 3 months. CONCLUSION The SMEDDS shows potential for enhancing the in vitro dissolution of NBH and demonstrates good stability.

Objective:To explore the advantages of minimally invasive internal fixation assisted by an orthopedic robot in the treatment of tibial plateau fractures of Schatzker types Ⅱ and Ⅲ that can be indirectly reduced.Methods:A retrospective study was conducted of the 18 patients who had been treated for tibial plateau fractures of Schatzker types Ⅱ and Ⅲ at Department of Orthopaedics, The Fourth Hospital of Wuhan from December 2019 to December 2021. They were 12 males and 6 females with an age of (45.2±9.6) years. All fractures were closed. Of them, 6 were complicated with an avulsion fracture at the insertion point of the anterior cruciate ligament, 1 with tear of the medial collateral ligament, and 8 with tear of the lateral meniscus. All patients were treated with minimally invasive internal fixation using the "fence" screw technique after indirect reduction assisted by an orthopedic surgical robot. Those combined with avulsion fracture of the anterior cruciate ligament and meniscus tear underwent one-stage arthroscopic surgery, while those combined with tear of the medial collateral ligament underwent one-stage open repair. The fracture reduction was evaluated according to the Rasmussen radiological scoring system, and the knee joint function evaluated using the American Hospital for Special Surgery (HSS) scoring system.Results:All the 18 patients were fully followed up for (10.6±1.9) months. The X-ray films immediately after surgery showed good fracture reduction. The fractures healed after (11.3±1.2) weeks. At 6 months after surgery, the Rasmussen knee score was (16.8±1.0) points, giving 5 excellent and 13 good cases; the HSS score was (93.2±3.0) points, giving 17 excellent and 1 good cases. By the last follow-up, no serious complications occurred, such as common peroneal nerve injury, popliteal vascular injury, postoperative infection, or internal fixation failure.Conclusion:Since minimally invasive internal fixation assisted by an orthopedic robot can lead to fine clinical efficacy for tibial plateau fractures of Schatzker types Ⅱ and Ⅲ, this technique can be widely applied in clinical practice.

Objective: Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with lightchain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA. Materials and Methods: In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49–63] years). Patients underwent longitudinal monitoring using biomarkers and CMR imaging. At followup after chemotherapy, patients were categorized into superior and inferior response groups based on their hematological and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapies and differences between response groups were analyzed. Results: Following chemotherapy (before vs. after), there were significant increases in myocardial T2 (43.6 ± 3.5 ms vs. 44.6 ± 4.1 ms; P = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%; P = 0.031), and decrease in RV extracellular volume fraction (ECV) (median of 53.9% vs. 51.6%; P = 0.048). These changes were more pronounced in the superior-response group. Patients with superior cardiac laboratory response showed significantly greater reductions in RV ECV (-2.9% [interquartile range, -8.7%–1.1%] vs. 1.7% [-5.5%–7.1%]; P = 0.017) and left ventricular ECV (-2.0% [-6.0%–1.3%] vs. 2.0% [-3.0%–5.0%]; P = 0.01) compared with those with inferior response. Conclusion Cardiac amyloid deposition can regress following chemotherapy in patients with AL-CA, particularly showing more prominent regression, possibly earlier, in the RV. CMR emerges as an effective tool for monitoring associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, thereby supporting its utility in treatment response assessment.

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.

Objective:To investigate the clinical efficacy of 3D printed osteotomy guide plate combined with "Jail" screw technique in the treatment of tibial plateau fractures involving external posterior condylar collapse.Methods:From January 2016 to January 2021, 41 patients (22 males and 19 females) with tibial plateau fractures involving external posterior condylar collapse were treated with 3D printed osteotomy guide plate combined with "Jail" screw technique and followed up. The age was 47.4±11.5 years (range, 22-69 years). According to Schatzker fracture type, 18 cases were type IV, 14 cases were type V and 9 cases were type VI. All fractures were closed, and 12 of them were complicated with lateral meniscus injury, but none of them were complicated with nerve and vascular injury. The time from injury to operation was 7.2±3.4 d (range, 4-17 d). All patients underwent 3D CT scanning and digital modeling before operation. According to the modeling results, a 1∶1 solid size fracture model was made by 3D printing, and the osteotomy guide plate and the "Jail" screw preset guide plate were designed. During the operation, the tibial lateral condyle osteotomy was performed with customized osteotomy guide plate. After reduction, the fixation of the fracture was performed with the preset guide plate using "Jail" screw. Postoperative fracture reduction was evaluated according to Rasmussen score, and knee function was evaluated by Hospital for Special Surgery (HSS) score.Results:All the 41 patients were followed up for 15.2±5.8 months (range, 6-26 months). Immediate postoperative radiographs showed good fracture reduction, and the average healing time was 14.1±1.2 weeks (range, 12-17 weeks). One year after operation, the Rasmussen score of knee joint was 17.4±1.6 points (range, 13-19 points), of which 31 cases were excellent, 8 cases were good, and 2 cases were fair, with an excellent/good rate of 95% (39/41). HSS scores was 87.3±5.6 points (range, 68-95 points), including 30 excellent cases, 10 good cases and 1 fair case, with an excellent/good rate of 98% (40/41). The range of motion of knee joint was 126.8°±3.8°. At the last follow-up, no serious complications such as common peroneal nerve injury, popliteal vascular injury, postoperative infection, or internal fixation failure occurred.Conclusion:3D printed osteotomy guide plate combined with "Jail" nail placement technique is an effective method for tibial plateau fractures involving external posterior condylar collapse, and the postoperative treatment results are satisfactory. The use of customized osteotomy guide plate is more accurate and less damaging. The use of "Jail" screw preset guide plate can ensure more accurate screw placement.

Objective:To compare the efficacy of fusion and non-fusion hybrid operation with Dynesys system with the traditional fusion operation with rigid instrumentation in the patients with multi-segment lumbar degenerative disease.Methods:A total of 30 patients with multi-segment lumbar degenerative disease who were subjected to operation from January 2017 to October 2019 in Shenzhen People's Hospital were included in the study. There were 13 males and 17 females, age: 60.8±13.2 years, range: 25 to 83 years. 28 patients with two segments, 1 with three segments, and 1 with four segments. The patients were divided into two groups, i.e the hybrid operation group (13 cases, 9 males and 4 females, average age: 56.6 years, range: 25 to 83 years) versus the traditional fusion group (17 cases, 4 males and 13 females, average age: 63.9 years, range: 46 to 80 years). The main outcome measures were visual analogue scale (VAS), Oswestry disability index (ODI), range of motion (ROM), adjacent segment degeneration (ASD) and complications.Results:There were no statistically significant differences in operation data, such as operation time, intraoperative blood loss, postoperative drainage volume and length of hospitalization, between the two groups. There were no significant differences for ROM in the surgical segments between the two groups before operation (hybrid group and traditional group were 9.6°±4.9° vs. 8.9°±6.1°, t=0.341, P=0.736, respectively). However, after 12 months follow-up, the ROM disappeared in the traditional group and was partially preserved in the hybrid group, with statistically significant differences (hybrid group and traditional group were 5.4°±2.7° vs. 0°, t=9.104, P=0.001, respectively). There was a statistical difference in intervertebral disc height between the two groups at 12 months post-operation, though no statistical difference was found before operation (8.8±1.9 mm vs. 10.5±1.7 mm, t=2.927, P=0.006). There was no statistically significant difference in the intervertebral disc height of the upper adjacent vertebrae between the two groups before and after operation. There were statistically significant differences in ODI scores before operation (63.4%±11.0% vs. 71.3%±9.2%, t=2.146, P=0.041), and 12 months post-operation (17.2%±2.1% vs. 15.5%±2.3%, t=2.091, P=0.046), while no statistical difference was found in VAS scores. Conclusion:The fusion and non-fusion hybrid operation with Dynesys system has comparable clinical efficacy with the traditional fusion operation with rigid instrumentation in the treatment of multisegment lumbar degenerative disease. Meanwhile, the hybrid surgery can preserve the motion of surgical segments and provide a dynamic stability of the vertebral body. The hybrid surgery can be used as a new surgical method for multi-segment lumbar degenerative disease.

Objective To investigate the effect of lower thoracic epidural block on intestinal epithelial cell apoptosis during hemorrhagic shock and resuscitation in rats.Methods Sixty-four male SD rats placed with lower thoracic epidural catheter were randomly divided into four groups (n=1 6 each):group Sham (sham operation),group HSR (hemorrhagic shock and resuscitation),group NS (hemorrhagic shock and resuscitation+epidural saline 100 μl/kg),and group TEA (hemorrhagic shock and resuscitation+epidural 0.075% ropivacaine 100 μl/kg).The hemorrhagic shock was made described by Chaudry.Rats were resuscitated by transfusing shed blood and normal saline 60 min after hemorrhagic shock.Malondialdehyde (MDA)content,superoxide dismutase (SOD)activity, and protein expression of Bax and Bcl-2 in intestinal epithelium were detected,and epithelial apoptosis index was calculated at 2 h after resuscitation.Results Compared with group Sham,intestinal epithe-lial MDA,Bax expression and epithelial apoptosis were significantly increased,while SOD activity were markedly decreased in groups HSR,NS and TEA (P<0.05).Compared with groups HSR and NS,intestinal epithelial MDA,Bax expression and epithelial apoptosis were significantly decreased, while SOD activity and Bcl-2 expression were markedly increased in group TEA (P <0.05 ). Conclusion Lower thoracic epidural block can enhance the antioxidant and anti-apoptotic ability,and inhibit the oxidative stress and cell apoptosis of intestinal epithelium.Therefore,it can promote the survival rate after hemorrhagic shock and resuscitation through protecting intestinal barrier.

Objective: To analyze the clinical effect of the endoscopic holistic rhinoplasty in order to improve its clinical application and safety. Methods: The patients with external nasal deformities and complained nasal congestion were assessed before operation and undergoing endoscopic holistic rhinoplasty from January 2015 to June 2017. Therefore, the internal nasal plasty and external nasal plasty were performed simultaneously, so as to correct the abnormalities of internal and external nasal structures, restore nasal ventilation function, and achieve the purpose of external nose cosmetology. The nasal congestion, visual analog scale, rhinomanometry and acoustic rhinometry and patient satisfaction were used to assess the efficacy. SPSS 21.0 was used for statistical analysis. Paired sample t test was used for preoperative and postoperative comparison, and P<0.05 was taken as statistically significant difference. Results: All the patients were followed up from one month to one year without complications. Postoperative nasal obstruction VAS score (1.63±0.76) was significantly lower than preoperative(6.35±0.65) (t=6.315, P<0.001). The minimum nasal cross-sectional area was (0.38±0.29) cm² preoperatively and (0.52±0.14) cm² postoperatively, which was significantly higher than that before the operation (t=9.732, P<0.001). Postoperative nasal volume (9.21±3.23) cm³ was significantly higher than preoperative (6.44 ± 1.04) cm³ (t=9.559, P<0.001), and postoperative nasal resistance (0.26 ± 0.07) kPa·s/L was lower than preoperative (0.65±0.21) kPa·s/L(t=7.524, P<0.001). The postoperative satisfaction survey result were very satisfactory in 41 cases (78.85%), accounted satisfaction in 11 cases (21.15%). Conclusions The application of the endoscopic holistic rhinoplasty has a good clinical effect and a high degree of satisfaction.

Objective To investigate the clinical efficacy of 3D printing technique combined with osteotomy in the treatment of complex tibial plateau fractures involving the posterolateral condyle.Methods The clinical data of 47 patients with complicated tibial plateau fractures involving the posterolateral condyle who were treated with 3D printing technology and tibial lateral condyle osteotomy from January 2012 to February 2015 were retrospectively analyzed.There were 19 males and 28 females aged from 21 to 69 years (mean 50.3 years).All of them were closed fractures without neurological and vascular injuries.The time between injury and operation was 4 to 19 days (average,6.7 days).All the patients were treated with tibial lateral condyle osteotomy and bilateral plate fixation with anterolateral approach and posteromedial approach.Three-dimensional CT scans were performed preoperatively and 1 ∶ 1 to mimics model was made by 3D printing technique based on the data after conversion.Refer to the 3D fracture model to accurately design the osteotomy line to improve the operation scheme.During the operation,anterior and lateral anterior combined with posterior medial incision were performed,and the tibia external condyle osteotomy was conducted to accurately expose the external posterior condyle fracture block of the tibia platform,and bilateral plate was applied after reduction.The fracture reduction was evaluated according to the Rasmussen score of the knee joint.The knee joint function was evaluated by the score of the hospital for special surgery (HSS).Results All 47 patients were followed up for 13.2 months (range,7-19 months).Immediate postoperative X-ray showed good fracture reduction.The union time of fracture was 14.3 weeks (range,12-18 weeks).The knee joint Rasmussen score one year after operation was 13-18 (average,15.73),including 33 cases excellent,12 cases good and 2 cases fair.The excellent and good rate was 95.7％ (45/47).HSS score was 67 to 94 (average,82.67),among which 31 cases were excellent,13 cases good,2 cases fair,and 1 case poor (postoperative refusal to rehabilitate exercise resulted in joint stiffness).The excellent and good rate of 89.9％ (44/47).Knee joint activity was-5°-0°-135°,with the average range of 125.5°.No common peroneal nerve injury,important vascular injury,postoperative infection,internal fixation failure and other serious complications was found.Conclusion 3D printing technology can help to accurately display the specific situation of the posterior tibial condyle fractures,which is conducive to the surgeon to develop a more intuitive plan of reduction.The method of tibial lateral condyle osteotomy can clearly reveal the tibial plateau posterolateral condylar fractures.With accurate osteotomy the surgical field can be fully exposed,and ultimately achieve a satisfactory result.Therefore,3D printing combined with tibial lateral condyle osteotomy is an effective method for complex tibial plateau fractures involving the posterolateral condyle.