Network pharmacology-based study on mechanism of Zhi-Huang-Zhi-Tong powder in rheumatoid arthritis treatment / 中国药理学通报

Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

Injectable and Cell-Laden Hydrogel in the Contained Bone Defect Animal Model: A Systematic Review

BACKGROUND@#Due to its high water content and biomimetic properties simulating extracellular matrix (ECM), hydrogels have been used as preferred cell culture and delivery systems. Similarly, cell-loaded hydrogels can be easily injected into target areas in a minimally invasive manner, minimizing surgical trauma, adapting to irregular shaped defects, and benefiting patients. In this study, we systematically reviewed multiple studies on hydrogel-based bone defect research and briefly summarized the progress of injectable and cell-loaded hydrogels in bone defect repair. @*METHODS@#A systematic search was conducted in the PubMed and Web of Science databases using selected search terms. @*RESULTS@#Initially, 185 articles were retrieved from the databases. After full-text screening based on inclusion and exclusion criteria, 26 articles were included in this systematic review. Data collected from each study included culture model, seed cell type and origin, cell concentration, scaffold material, scaffold shape, experimental animal and site, bioactive agents, and binding method. This injectable and cell-loaded hydrogel shows certain feasibility in bone tissue engineering applications. @*CONCLUSION@#Injectable and cell-loaded hydrogels have been widely applied in bone tissue engineering research. The future direction of bone tissue engineering for bone defect treatment involves the use of new hydrogel materials and biochemical stimulation.

Regulation of platelet function by cantharidin via PI3K/Akt/PKC pathway / 中国药理学通报

To investigate the effect of cantharidin ( CTD) on platelet function and the mechanism of anti-platelet aggregation. Methods Washed platelets were collected from the venous blood of healthy volunteers. The effect of CTD on platelet aggregation and release was determined by aggregometer. The CTD concentration was 2.5 ,5 ,10 μmol • L

Comparison of a novel kind of anatomical locking plate versus proximal humeral internal locking system in treatment of proximal humerus fractures / 中华创伤骨科杂志

Objective:To compare a novel kind of anatomical locking plate versus proximal humeral internal locking system (PHILOS) in the treatment of proximal humerus fractures.Methods:A retrospective study was performed in the 35 patients with proximal humerus fracture who had been operatively treated at Department of Orthopedics, The Third Hospital of Peking University from January 2020 to June 2021. They were 13 males and 22 females, aged from 24 to 83 years (average, 56.7 years). Of them, 14 were fixated by the novel anatomical locking plate and 21 by PHILOS. The 2 groups were compared in terms of gender, age, fracture type, operation time, intraoperative blood loss, hospital stay, University of California (UCLA) shoulder scores and Disability of Arm Shoulder and Hand (DASH) scores for the upper limb dysfunction at one month after operation and at the last follow-up, and postoperative complications.Results:There was no significant difference in the preoperative general data between the novel plate group and the PHILOS group, showing comparability between them ( P>0.05). All the patients were followed up for 6 to 21 months (mean, 11.3 months). In the novel anatomical plate group, the operation time was (83.9±29.2) min, the intraoperative blood loss was (36.4±27.1) mL, the hospital stay was (2.3±1.1) d, the UCLA score and DASH score at one month after operation were (20.1±4.7) points and (55.5±19.1) points, the UCLA score and DASH score at the last follow-up were (28.5±4.6) points and (25.1±24.4) points, respectively; 2 patients developed complications after operation. In the PHILOS group, the operation time was (85.0±38.8) min, the intraoperative blood loss was (62.9±46.8) mL, the hospital stay was (2.4±0.9) d, the UCLA score and DASH score at one month after operation were (21.0±3.8) points and (49.6±23.7) points, and the UCLA score and DASH score at the last follow-up were (28.0±5.1) points and (19.1±17.3) points, respectively; 3 patients developed complications after operation. There was no significant difference in all the above items between the 2 groups (all P>0.05). Conclusion:In the treatment of proximal humerus fractures, the novel anatomical locking plate is a feasible internal fixator because it is comparable to PHILOS in fine efficacy, good fracture healing, and satisfactory functional recovery of the shoulder joint.

Comparison of percutaneous cannulated screw fixation and plating via minimally invasive longitudinal approach after closed reduction in treatment of intra-articular tongue-type calcaneal fractures / 中华创伤骨科杂志

Objective:To compare percutaneous cannulated screw (PCS) fixation and plating via a minimally invasive longitudinal approach (MILA) after closed reduction for the treatment of intra-articular tongue-type calcaneal fractures.Methods:A retrospective analysis was conducted of the 67 patients with intra-articular tongue-type calcaneal fracture who had been treated at Department of Orthopedics, The Third Hospital of Peking University from May 2017 to May 2020. They were 56 males and 11 females, 19 to 58 years of age (average, 34.5 years). Of them, 32 were treated by the PCS fixation after closed reduction (PCS group) and 35 by the MILA plating after closed reduction (MILA group). The operation time, preoperative time, post-operative hospital stay, blood loss and postoperative complications were recorded and compared between the 2 groups. The calcaneal length, width and height, Gissane angle, B?hler angle, varus angle, valgus angle and visual analog scale (VAS) were compared between the 2 groups at preoperation, immediate postoperation, 3 months postoperation, and the last follow-up. The American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score was used at 3 months postoperation and the last follow-up to evaluate the function of the injured hindfoot.Results:There was no significant difference in the preoperative general data between the PCS group and the MILA group, showing they were comparable ( P>0.05). All patients were followed up for an average of 18.5 months (from 15 to 25 months). For the PCS group and the MILA group, respectively, the operation time was 60.5 (51.5, 68.0) min and 86.0 (78.0, 96.0) min, the blood loss 10 (5.0, 20.0) mL and 20 (15, 25) mL, the postoperative hospital stay 1 (1.0, 1.8) d and 2 (2, 3) d, the calcaneal width at immediate postoperation (43.8±4.4) mm and (40.6±2.8) mm, the calcaneal width at 3 months postoperation 43.8 (39.6, 48.3) mm and 41.5 (38.8, 44.5) mm, the calcaneal width at the last follow-up 44.2 (40.2, 48.0) mm and 41.3 (39.0, 44.3) mm, the VAS at the last follow-up 5.0 (5.0, 5.0) and 6.0 (5.0, 6.0). The comparisons of the above items showed significant differences between the 2 groups (all P<0.05). No significant differences were observed between the 2 groups in the calcaneal length or height, Gissane or B?hler angle, AOFAS hindfoot score, or complication rate (all P>0.05). Conclusions:In the treatment of tongue-type calcaneal fractures, after closed reduction, the PCS fixation can shorten operation time and postoperative hospital stay, and reduce intraoperative blood loss and postoperative pain, but the MILA plating is more advantageous in restoring the calcaneal width.

Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (version 2022) / 中华创伤杂志

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Erianin inhibits oral cancer cell growth, migration, and invasion via the Nrf2/HO-1/ GPX4 pathway

Objective: To evaluate the effect of erianin on the viability, migration, and invasion of KB cells and elucidate its underlying mechanisms. Methods: Cell Counting Kit-8, colony formation, wound healing, and Transwell assays were used to determine the proliferation, migration, and invasion of oral cancer KB cells. Furthermore, malondialdehyde (MDA) and glutathione (GSH) levels were determined. Fluorescent probes were used to detect changes in intracellular reactive oxygen species and iron ions. Additionally, the expressions of ferroptosis-related proteins, NF-E2-related factor 2 (Nrf2), ferritin heavy chain 1 (FTH1), heme oxygenase 1 (HO-1), and glutathione peroxidase 4 (GPX4) were analyzed by Western blotting assays. Results: Erianin induced ferroptosis and inhibited the proliferation, migration, and invasion of KB cells. Moreover, erianin decreased GSH level, increased MDA level, elevated intracellular ROS and Fe

Casticin inhibits the proliferation, migration and invasion of bladder cancer cells by inhibition of TM7SF4 expression / 中华肿瘤杂志

Objective: To explore the effect and mechanism of Casticin (CAS) on the proliferation, migration and invasion of bladder cancer T24 cells. Methods: T24 cells were cultured in vitro and divided into control group, 5, 10, 20 μmol/L CAS groups, si-NC group, si-TM7SF4 group, CAS+ pcDNA group and CAS+ pcDNA-TM7SF4 group. Cell counting kit-8 (CCK-8) was used to detect cell proliferation; Transwell was used to detect cell migration and invasion; western blot was used to detect the protein expressions of cyclin D1, p21, MMP-2, MMP-9 and TM7SF4, and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of TM7SF4 mRNA. Results: The inhibition rates of T24 cells in the 5, 10, 20 μmol/L CAS groups were (17.68±1.41)%, (33.54±3.16)% and (61.44±5.50)%, respectively, higher than (0.00±0.00)% of the control group (P<0.001), but the numbers of migration and invasion were 72.83±5.66, 59.13±4.27, 41.25±3.22 and 55.83±5.15, 42.19±3.06, 31.13±3.22, respectively, lower than 86.11±5.16 and 68.82±5.29 of the control group (P<0.001). The protein expression levels of cyclin D1, MMP-2, MMP-9, TM7SF4 and the expression levels of TM7SF4 mRNA in the 5, 10, and 20 μmol/L CAS groups were lower than the control group (P<0.001). However, the protein expression levels of p21 were 0.37±0.03, 0.51±0.04, and 0.66±0.06, respectively, higher than 0.25±0.03 in the control group (P<0.001). The inhibition rate of T24 cells in the si-TM7SF4 group was (50.35±4.67)%, higher than (6.31±0.58)% in the si-NC group (P<0.001), but the numbers of migration and invasion were 53.51±4.18 and 42.92±3.81, lower than 85.26±4.99 and 67.93±4.64 of the si-NC group (P<0.001). The protein expression levels of TM7SF4, CyclinD1, MMP-2, MMP-9 in the si-TM7SF4 group were lower than the si-NC group (P<0.001). However, the protein expression level of p21 in the si-TM7SF4 group was higher than the si-NC group (P<0.001). The inhibitory rate of T24 cells in the CAS+ pcDNA-TM7SF4 group was (21.45±2.46)%, lower than (64.06±4.49)% of the CAS+ pcDNA group (P<0.001), but the number of migration and invasion in the CAS+ pcDNA-TM7SF4 group were 75.66±6.57 and 59.35±5.40, higher than 40.43±3.85 and 30.25±3.32 in the CAS+ pcDNA group (P<0.001). The protein expression levels of TM7SF4, CyclinD1, MMP-2 and MMP-9 in the CAS+ pcDNA-TM7SF4 group were higher than the CAS+ pcDNA group (P<0.001), but the protein expression level of p21 was lower than the CAS+ pcDNA group (P<0.001). Conclusion: CAS may suppress the proliferation, migration and invasion of bladder cancer T24 cells by inhibiting the expression of TM7SF4.

Clinical effects of 3D printed porous titanium-alloy prosthesis in reconstruction of long bone defects of lower extremities / 中华骨科杂志

Objective:To analyze and summarize the clinical effects of 3D printed porous titanium-alloy prosthesis implantation in the treatment of long bone defects of lower extremities.Methods:We retrospectively studied the clinical cases with lower extremity bone defect treated by 3D printed porous titanium prostheses from December 2017 to November 2021. 18 patients who were followed up for more than 12 months were included in this study. The enrolled patients included 12 males and 6 females, with an average of 48.9±22.5 years (range, 13-79 years), and an average body mass index of 23.1±4.3 kg/m 2 (range, 17.2-27.1 kg/m 2). There were 14 osteomyelitis-derived bone defects and 4 nonunion-derived bone defects. The bone defect locations included 10 cases of femur and 8 cases of tibia. The average bone defect distance was 13.9±9.7 cm (range, 5.8-31.2 cm), and the proportion of the defect length to the long bone (femur of tibia) was average 33.7%±16.8% (range, 15.0%-63.0%). The clinical efficacy was comprehensively evaluated through gross observation, imaging evaluation, changes in the total length of lower extremities and long bones, femorotibial angle (FTA) measurement, lower extremity functional scale (LEFS), satisfaction, complications and other indicators, focusing on the stabilization mechanism of the prosthesis and the regeneration of new bone. Results:All 18 patients were followed up for 12-35 months, with an average of 16.3 months. Postoperative X-rays at 1, 3, 12 and 24 months showed that new bone could gradually creep along the prosthesis surface. The preoperative bone defect length of long bone and total length of lower limb were respectively 39.4±4.0 cm and 80.5±5.7 cm, which were different from those of the healthy side by 1.6±1.0 cm and 1.5±1.1 cm. One week after implantation, the length of long bone and lower limb was 39.9±3.5 cm and 80.9±6.2 cm, respectively, and the average difference was 1.0±0.6 cm and 0.9±1.1 cm compared with the healthy side. At the last follow-up, the length of long bone and lower limb was 39.7±3.6 cm and 80.9±7.8 cm, with an average difference of 1.8±1.1 cm and 1.0±0.7 cm from the healthy side. There were no significant differences in the length of long bone and lower limbs at the three time points before surgery, one week after surgery and the last follow-up ( F=0.12, 0.04; P>0.05). The average FTA of the affected limb was 174.7° (173.9°, 175.5°), 175.2°(173.5°, 176.4°), and 175.0°(173.5°, 176.3°) at three time nodes, before surgery, one week after surgery and the last follow-up, respectively, and there was no significant statistical difference in pairwise comparison ( Z=0.01, P>0.05). Patients had a mean LEFS score of 50 (46, 51) at the last follow-up, significantly higher than the preoperative score of 20 (17, 21) ( Z=-5.56, P<0.001). The mean satisfaction score of the 18 patients at the last follow-up was 9.7. Two patients (11.1%) had screw fractures but all 3D printed porous titanium alloy prostheses remained stable without significant loosening or displacement. Two patients (11.1%) had nail channel infection of external fixator, all patients with channel infection were cured by intravenous antibiotics combined with local disinfection and dressing change. Conclusion:The implantation of 3D printed porous titanium-alloy prosthesis could efficiently and safely repair the long bone defects of the lower extremities. The prosthesis could maintain stable in the early and middle postoperative period. The length of the long bones and lower limbs did not change significantly with the weight-bearing and functional exercise of the limbs. The new bone could gradually crawl and grow from both ends of the defect, and the patient's limb function recovered significantly, and the patient's satisfaction was high.

An axillary approach for open reduction and internal fixation to treat anterior glenoid fracture: an anatomical and clinical study / 中华骨科杂志

Objective:To investigate the clinical effect and safety of reduction and fixation for the anterior glenoid fracture through an axillary approach.Methods:Two autopsy specimens (a total of 4 shoulder joints) were used to simulate the surgery of open reduction and internal fixation to treat anterior glenoid fracture through an axillary approach. Specimens were placed in the lateral decubitus position. An incision was made in the posterior axillary line to expose the lateral side of the scapula through the interval ahead of the latissimus dorsi muscle. Attended to the separation and protection of the axillary nerve, posterior humerus artery, thoracic dorsal nerve, and scapular artery. The surgical area of the axillary approach was divided into the upper "quadrilateral area" and the lower "trilateral area", which exposed the anteroinferior glenoid, neck, and the full length of lateral border of the scapula. Thirteen cases (7 males and 6 females) were involved in this study, all patients were diagnosed with anterior glenoid fracture and treated by open reduction and internal fixation through the axillary approach between April 2018 and December 2020. Constant-Murley score and Disabilities of the Arm, Shoulder and Hand (DASH) were used to evaluate the clinical efficacy.Results:Thirteen patients were enrolled for final analysis, which included 12 right cases and 1 left case. The average age was 50.38±13.74 years (range 24-67 years). All 13 patients were classified as Ideberg type Ia fracture. Anatomical buttress plates were used in 5 cases, cannulated screws combined with metacarpal plates in 7 cases, and distal radius plate in 1 case. The average length of follow-up was 13.00±5.97 months (range 6-26 months). No delayed union or malunion in all cases at the last follow-up visits. The average of Constant-Murley score was 62.46±10.26 points (range 45-83) and the DASH score was 27.56±9.76 points (range 14.14-43.33) at the three months follow up visits. At 6 months postoperatively, the Constant-Murley score was 80.85±8.32 points (range 65 to 90) and the DASH score was 11.47±8.56 points (range 0 to 35.00). Constant-Murley score at the final patient's follow-up visit was 84.54±8.95 points (range 70-95), and the DASH score was 10.94±8.67 points (range 1.67 to 33.33 points). The joint function gradually recovered with time. The functional scores at 3 months, 6 months after surgery, and final follow-up visit had significant differences ( P<0.05). Conclusion:The axillary approach is a safe and feasible approach for the treatment of the anterior glenoid fracture. This approach exposes the anteroinferior glenoid and the lateral border of the scapula, which reduces rotator-cuff injury and achieves anatomic reduction and strong fixation of the fracture. The axillary approach surgery also allows early functional physiotherapy after surgery.

Posterior axillary approach for treatment of some scapular fractures / 中华创伤骨科杂志

Objective:To investigate the efficacy of the posterior axillary approach in the treatment of some scapular fractures.Methods:Retrospectively analyzed were the data of 41 patients with scapular fracture who had been treated through the posterior axillary approach at Department of Traumatology, The Second Hospital of Jilin University from April 2018 to July 2021. There were 32 males and 9 females, aged from 24 to 83 years (average, 52.4 years). Of them, 7 were complicated with multiple injuries, 16 with other fractures, and 4 with brachial plexus injury. Recorded were length of surgical incision, intraoperative blood loss, operation time, and range of shoulder motion, Disability of Arm Shoulder and Hand (DASH) score, Constant shoulder score and postoperative complications at the last follow-up.Results:In this cohort, length of incision ranged from 7 to 12 cm (average, 9.3 cm), intraoperative blood loss from 80 to 150 mL (average, 110.5 mL), exposure time of the posterior axillary approach from 5 to 10 min (average, 7.9 min), and fracture operation time from 85 to 140 min (average, 110.8 min). The 41 patients were followed up for 6 to 36 months (mean, 14.3 months) after surgery. At the last follow-up, the average ranges of shoulder motion were 177° (from 150° to 180°) in flexion, 175° (from 140° to 180°) in abduction and 47° (from 30° to 50°) in extension, the average DASH score was 36.4 points (from 34 to 46 points), and the average Constant score 96.0 points (from 84 to 100 points). There were no complications like loss of fracture reduction, loosening or breakage of plate or screw during follow-up. Incision healing was delayed in 2 patients and mild heterotopic ossification occurred in 2 patients.Conclusion:As a new surgical approach for some scapular fractures, the posterior axillary approach allows internal fixation of the fractures of the scapular glenoid, neck and body under direct vision, leading to good-looking postoperative wound and reliable curative effects.

Macrophage Activation Induced by TMAO through CD147 / MMPs / 中国生物化学与分子生物学报

Trimethylamine N-oxide (TMAO), a metabolite of intestinal flora, can promote Atherosclerosis (AS) in various ways. Current studies have found that it has a close relationship with plaque stability in clinical practice, but its molecular mechanism remains unclear at present. Extracellular matrix metalloproteinase inducers (CD147) / matrix metalloproteinases (MMPs) regulate a signal pathway highly related to plaque stability, which can promote plaque instability and lead to cardiovascular adverse events by weakening the thickness of the fibrous cap. Therefore, in this study, the mouse macrophageRAW264. 7 was stimulated by TMAO to establish a cell model to observe the effects on CD147, MMP2, and MMP9, and the CD147 gene silencing model was further constructed by using the siRNA transfection method to explore the interaction between CD147 and MMP2 and MMP9. Rt-qPCR and Western blotting results showed that there was no significant change in the gene expression level of CD147 in mouse macrophage RAW264. 7, but significantly increased in protein levels (P < 0. 05), while MMP2 andMMP9 were increased in mRNA and protein levels (P<0. 05). The expression of CD147, MMP2, andMMP9 was significantly inhibited in CD147 siRNA transfected cells (P<0. 05). In conclusion, TMAO significantly increases the expression of MMP2 and MMP9 in mouse macrophages RAW264. 7, and this effect may be partially realized through the CD147/ MMP pathway.

Berberine inhibits erastin-induced ferroptosis of mouse hippocampal neuronal cells possibly by activating the Nrf2-HO-1/GPX4 pathway / 南方医科大学学报

OBJECTIVE@#To explore the mechanism by which berberine inhibits ferroptosis of mouse hippocampal neuronal cells (HT22).@*METHODS@#Cultured HT22 cells were pretreated with 30 or 60 μmol/L berberine for 2 h before exposure to 0.5 μmol/L erastin for 8 h, and the cell proliferation, intracellular ferric iron level, changes in intracellular reactive oxygen species (ROS) and cell apoptosis were detected using CCK-8, Fe2+ fluorescent probe, fluorescent dye (DAPI) and fluorescent probe (H2DCFH-DA). RT-qPCR and Western blotting were used to detect the mRNA and protein expressions of Nrf2, HO-1 and GPX4 in the cells. We further tested the effects of treatments with 2 μmol/L ML385 (a Nrf2 inhibitor), 60 μmol/L berberine and erastin in the cells to explore the protective mechanism of berberine against erastin-induced ferroptosis in the neuronal cells.@*RESULTS@#Treatment with 0.5 μmol/L erastin significantly lowered the viability of HT22 cells (P < 0.05) and increased the production of ROS, cell apoptosis rate and ferric iron level (P < 0.05). Pretreatment with 30 and 60 μmol/L berberine both significantly increased the vitality of erastin-exposed cells (P < 0.05) and lowered the levels of intracellular ROS and ferric iron content (P < 0.05). RT-qPCR and Western blotting showed that berberine obviously promoted the expressions of Nrf2, HO-1 and GPX4 in the cells (P < 0.05), and treatment with ML385 significantly inhibited the Nrf2-HO-1/GPX4 pathway, increased intracellular ROS and ferric iron contents and mitigated the protective effect of berberine against erastin-induced ferroptosis (P < 0.05).@*CONCLUSION@#Berberine can inhibit erastin-induced ferroptosis in HT22 cells possibly by activating the Nrf2-HO-1/ GPX4 pathway.

Molluscicidal activity of the secondary metabolites from Streptomyces nigrogriseolus XD 2-7 against Oncomelania hupensis and its preliminary mechanisms of molluscicidal actions / 中国血吸虫病防治杂志

OBJECTIVE@#To evaluate the storage stability of metabolites from actinomycetes Streptomyces nigrogriseolus XD 2-7 and the mollcuscicidal activity against Oncomelania hupensis in the laboratory, and to preliminarily explore the mechanisms of the molluscicidal activity.@*METHODS@#The fermentation supernatant of S. nigrogriseolus XD 2-7 was prepared and stored at -20, 4 °C and 28 °C without light for 10 d; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation supernatant was boiled in a 100 °C water bath for 30 min and recovered to room temperature, and then the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The pH values of the fermentation supernatant were adjusted to 4.0, 6.0 and 9.0 with concentrated hydrochloric acid and sodium hydroxide, and the fermentation supernatant was stilled at room temperature for 12 h, with its pH adjusted to 7.0; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation product of S. nigrogriseolus XD 2-7was isolated and purified four times with macroporous resin, silica gel and octadecylsilane bonded silica gel. The final products were prepared into solutions at concentrations of 10.00, 5.00, 2.50, 1.25 mg/L and 0.63 mg/L, and the molluscicidal effect of the final productswas tested against O. hupensis following immersion for 72 h, while dechlorination water served as blank controls, and 0.10 mg/L niclosamide served as positive control. The adenosine triphosphate (ATP) and adenosine diphosphate (ADP) levels were measured in in O. hupensis soft tissues using high performance liquid chromatography (HPLC) following exposure to the final purified fermentation products of S. nigrogriseolus XD 2-7.@*RESULTS@#After the fermentation supernatant of S. nigrogriseolus XD 2-7 was placed at -20, 4 °C and 28 °C without light for 10 d, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100% (30/30) O. hupensis mortality. Following boiling at 100 °C for 30 min, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100.00% (30/30) O. hupensis mortality. Following storage at pH values of 4.0 and 6.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 100.00% (30/30) O. hupensis mortality, and following storage at a pH value of 9.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 33.33% (10/30) O. hupensis mortality (χ2 = 30.000, P < 0.05). The minimum concentration of the final purified fermentation products of S. nigrogriseolus XD 2-7 was 1.25 mg/L for achieving a 100% (30/30) O. hupensis mortality. The ATP level was significantly lower in O. hupensis soft tissues exposed to 0.10 mg/L and 1.00 mg/L of the final purified fermentation products of S. nigrogriseolus XD 2-7 than in controls (F = 7.274, P < 0.05), while no significant difference was detected in the ADP level between the treatment group and controls (F = 2.485, P > 0.05).@*CONCLUSIONS@#The active mollcuscicidal ingredients of the S. nigrogriseolus XD 2-7 metabolites are maintained stably at -20, 4 °C and 28 °C for 10 d, and are heat and acid resistant but not alkali resistant. The metabolites from S. nigrogriseolus XD 2-7 may cause energy metabolism disorders in O. hupensis, leading to O. hupensis death.

Effects of praziquantel isomers on the proliferation and activation of the LX-2 human hepatic stellate cell line / 中国血吸虫病防治杂志

Objective To compare the effects of levo-praziquantel (L-PZQ) and dextro-praziquantel (D-PZQ) on the proliferation and activation of the human hepatic stellate cell line LX-2 in vitro. Methods LX-2 cells were stimulated with transforming growth factor-β (TGF-β). LX-2 cell proliferation was measured using the CCK-8 assay after 24 h stimulation with 0 to 50 μg/mL concentrations of praziquantel, and the gene and protein expression of type Ⅰ collagen (collagen Ⅰ), type Ⅲ collagen (collagen Ⅲ) and α-smooth muscle actin (α-SMA) was quantified in LX-2 cells using quantitative real-time PCR (qPCR) and Western blotting assays 24 h and 48 h following stimulation with 15 μg/mL praziquantel to detect LX-2 cell activation. Results There were significant differences in the survival rate of LX-2 cells between L-PZQ and D-PZQ treatments at all concentrations (F = 6.119 and 79.180, both P values < 0.05). Either L-PZQ or D-PZQ at a concentration of < 30 μg/mL showed no remarkableeffectsonthe LX-2 cell proliferation (both P values > 0.05), and L-PZQ at a concentration of > 50 μg/mL and D-PZQ at a concentration of > 40 μg/mL inhibited the LX-2 cell proliferation (both P values < 0.05), while D-PZQ at concentrations of 40 μg/mL and 50 μg/mL showed greater inhibition on LX-2 cell proliferation than L-PZQ (t = 3.419 and 8.776, both P values < 0.05). There were significant differences in the collagen Ⅰ, collagen Ⅲ and α-SMA expression in LX-2 cells at both transcriptional (F = 21.55, 79.99 and 46.70, all P values < 0.05) and translational levels (F = 20.12, 30.29 and 32.93, all P values < 0.05) among the blank control group, TGF-β stimulation group, L-PZQ treatment group and D-PZQ treatment group. L-PZQ treatment resulted in remarkable inhibition on collagen Ⅲ and α-SMA gene expression in LX-2 cells (both P values < 0.05); however, the treatment showed no remarkable inhibition collagen Ⅰ gene expression or collagen Ⅰ, collagen Ⅲ or α-SMA protein expression in LX-2 cells (all P values > 0.05). In addition, D-PZQ treatment resulted in significant inhibition on collagen Ⅰ, collagen Ⅲ and α-SMA expression in LX-2 cells at both translational and transcriptional levels (all P values < 0.05), and D-PZQ showed higher inhibition on collagen Ⅰ, collagen Ⅲ and α-SMA gene expression in LX-2 cells than L-PZQ (all P values < 0.05). Conclusions Both L-PZQ and D-PZQ inhibit the proliferation and activation of LX-2 cells, and D-PZQ shows a higher inhibitory activity than L-PZQ.

Research progress and prospects for the use of plant metabolomics in quality evaluation of traditional Chinese medicinal materials / 药学学报

The quality of traditional Chinese medicine has a direct impact on the effectiveness and safety of its use, and is the premise necessary to ensure the healthy development of the traditional Chinese medicine industry. Comprehensive and accurate control and evaluation of the quality of medicinal materials is of great significance to the traditional Chinese medicine industry, but the complexity and dynamics of the chemical composition of medicinal materials makes their quality evaluation a challenge. Plant metabolomics provides an integrated and comprehensive analysis that is consistent with the holistic approach of traditional Chinese medicine. Chemical information therein promotes the establishment of a traceable system and provides new ideas and methods for the quality evaluation of medicinal materials. Plant metabolomics in the quality evaluation of medicinal materials is gradually increasing, and the core is the screening and identification of differential metabolites or specific marker compounds by means of stoichiometry. This study focused on the main factors that affect the quality of medicinal materials, such as origin, environmental adversity, varieties, harvest time, commercial specification and TCM processing. We describe the research progress in plant metabolomics combined with chemometrics analysis for the quality control and evaluation of medicinal materials, summarize existing problems, identify trends, and propose future research directions. Metabolomics plays an increasingly important role in the quality evaluation of medicinal materials, but the absolute qualitative and quantitative information of metabolomics needs to be further developed, and a single 'omics' technique is not sufficient for an in-depth analysis of medicinal value. In the future, standardization of plant metabolomics methods and a more complete database should be actively promoted, and plant metabolomics should be integrated into quality marker exploration. Plant metabolomics will need to be integrated with other 'omics' methods to improve the quality and evaluation system of medicinal materials.

Activity of aromatic pyrrole-based compounds against of Schistosoma japonicum cercariae and acute toxicity to fish / 中国血吸虫病防治杂志

Objective To test the activity of aromatic pyrrole-based compounds against cercariae of Schistosoma japonicum and test their acute toxicity to fish. Methods A series of aromatic pyrrole-based compounds were synthesized using 4-benzyl-5-(trifluoromethyl)-1H-pyrrole-3-nitrile as the lead compound. The synthesized compounds were prepared into solutions at concentrations of 10.00, 1.00, 0.10, 0.01 mg/L, and the activity of these solutions against S. japonicum cercariae was tested in 30 min, while 0.10 mg/L and 0.01 mg/L niclosamide solutions served as a positive control and dechlorinated water with 1% dimethyl sulfoxide (DMSO) was used as a negative control, with 10 to 30 cercariae of S. japonicum in each group. In addition, the compounds were prepared into solutions at concentrations of 0.50, 0.25, 0.12, 0.06, 0.03 mg/L, and their toxicity to zebrafish was tested in 72 h, while 0.15 mg/L and 0.30 mg/L niclosamide solutions served as a positive control and dechlorinated water with 1% DMSO was used as a negative control, with 10 zebrafishes in each group. Results A total of 7 aromatic pyrrole-based compounds were successfully synthesized. Treatment with compounds 102, 104 and 106 at a concentration of 0.01 mg/L for 30 min killed all S. japonicum cercariae, and compounds 105 and 107 showed no activity against cercariae. No death of cercariae was found in the blank control group, while treatment with 0.10 mg/L niclosamide for 10 min caused a 100% mortality rate of S. japonicum cercariae and 0.01 mg/L niclosamide failed to kill S. japonicum cercariae. No zebrafish death was found 72 h post-treatment with compounds 101, 104 and 105 at a concentration of 0.03 mg/L, and exposure to compounds 102, 103 and 106 at a concentration of 0.03 mg/L for 12 h resulted in a 100% mortality rate of zebrafish. No zebrafish death occurred 72 h post-treatment with 0.50 mg/L Compound 104, and no zebrafish death was found in the blank control group, while treatment with 0.30 mg/L niclosamide for 24 h resulted in a 100% mortality rate of zebrafish. Conclusions Compound 104 achieves a 100% mortality rate against S. japonicum cercariae at a concentration of 0.01 mg/L for 30 min, and causes no death of zebrafish at a concentration of 0.50 mg/L for 72 h, which may serve as a cercaricide candidate.

Short-term outcomes of femoral neck system versus dynamic hip screws in treatment of femoral neck fractures / 中华创伤骨科杂志

Objective:To compare the short-term outcomes of femoral neck system (FNS) and dynamic hip screw (DHS) in the treatment of femoral neck fractures.Methods:A retrospective analysis was performed of the 105 patients with fresh femoral neck fracture who had been treated by FNS fixation from September 2019 to October 2020 or by DHS fixation from January 2018 to October 2020 at Department of Orthopaedics, The Third Hospital Affiliated to Peking University. In the FNS group of 54 cases, there were 18 males and 36 females with a mean age of (60.7±15.2) years; in the DHS group of 51 cases, there were 14 males and 37 females with a mean age of (63.3±13.2) years. The 2 groups were compared in terms of hospital stay, operation time, intraoperative blood loss, incision length, intraoperative fluoroscopy frequency, qualify of reduction, and femoral neck shortening length, Harris hip score and complications at the last follow-up.Results:The 2 groups were comparable due to insignificant differences in their preoperative general data or follow-up time ( P>0.05). In the FNS group, the median operation time [45.0 (40.0, 59.0) min], intraoperative blood loss [30.0 (20.0, 50.0) mL], incision length [4.0 (4.0, 5.0) cm], intraoperative fluoroscopy frequency [10.5 (9.0, 12.0) times] and hospital stay [2.0 (2.0, 4.0) d] were significantly superior to those in the DHS group [72.0 (55.0, 89.0) min, 50.0 (30.0, 50.0) mL, 7.0 (6.0, 8.0) cm, 18.0 (15.0, 19.0) times, and 3.0 (3.0, 6.0) d] (all P<0.05). There were no statistical differences between the 2 groups in quality of reduction, length of femoral neck shortening, failure rate of internal fixation or Harris hip score at the last follow-up ( P>0.05). There were no such surgical complications as deep infection or femoral head necrosis in either of the 2 groups. Conclusions:In the fixation of femoral neck fractures, both FNS and DHS may lead to fine short-term outcomes. However, compared with DHS, FNS exhibits advantages of simplicity, minimal invasion, less surgical trauma and intraoperative fluoroscopy frequency, and reduced operation time and hospital stay.

Effect evaluation on training mode based on core competence of nurses in clinical practice of nursing / 中华医学教育探索杂志

Objective:To explore the influence of training mode based on core competence of nurses on comprehensive performance, critical thinking ability and clinical communication ability of nursing students.Methods:A total of 102 Batch 2015 nursing students from the four-year program of Hubei University of Medicine who were interned in a "three A" general hospital in Shiyan City from May 2018 to January 2019 were selected as subjects, and were randomized into the control group ( n=51) and the intervention group ( n=51). The control group received traditional training mode and the intervention group adopted the training mode based on core competence of nurses. The two groups of nursing students were graded on the critical thinking scale and clinical communication ability scale before practice and at 2 months, 4 months, 8 months after intervention respectively. The comprehensive performance of two groups was assessed before and after 8 months of intervention. All data were analyzed by SPSS 19.0. Results:Comparison of effect, interaction effect, time effect of critical thinking scale and clinical communication ability scale between the two groups showed significant differences ( P<0.05). The comprehensive performance differences between the two groups were statistically significant after the intervention ( P<0.05). Conclusion:The practice training mode based on core competence of nurses can effectively improve the comprehensive performance, critical thinking ability and clinical communication ability of nursing students.

Studies on resistance of Schistosoma to praziquantel XVIII Sensitivity to praziquantel in filial generations of praziquantel-resistant and -sensitive Schistosoma japonicum mixed infections / 中国血吸虫病防治杂志

Objective To investigate the sensitivity of adult worms of filial generations from praziquantel-resistant and -sensitive Schistosoma japonicum mixed infections to praziquantel. Methods Mice were infected with the cercariae of an experimentally generated praziquantel-resistant S. japonicum isolate [median effective dose (ED50) = 277.4 mg/kg] and a laboratory-maintained praziquantel-sensitive S. japonicum isolate (ED50 = 99.6 mg/kg) at a mixture ratio of 1:1 and 2:1, which was maintained in the laboratory via the mouse-snail cycle for 8 generations. Then, mice were infected with the cercariae of the 8th filial-generation parasite, and grouped 35 days post-infection. Mice in the 5 treatment groups were given praziquantel treatment by gavage at a single oral dose of 37.5, 75, 150, 300 mg/kg and 600 mg/kg, while animals in the control group was administered orally with 2.5% cremophor EL. All mice were sacrificed 14 days post-treatment and adult worms were collected by perfusion of the portal vein. The worm burden reductions and praziquantel ED50 values were calculated. The praziquantel-resistant S. japonicum isolate generated from experimental induction with 12 rounds of praziquantel treatment with sub-curative doses was maintained in the laboratory via the mouse-snail cycle, and mice were infected with the cercariae of the 8th filial-generation parasite. The praziquantel ED50 value against the 8th filial-generation adults was measured. Results After mice were infected with the mixture of cercariae of PZQ-resistant and -sensitive S. japonicum isolates at a ratio of 1:1, the praziquantel ED50 was 135.2 mg/kg against the adults of the 8th filial-generation parasite. After mice were infected with the mixture of cercariae of PZQ-resistant and -sensitive S. japonicum isolates at a ratio of 2:1, the praziquantel ED50 was 129.2 mg/kg against the adults of the 8th filial-generation parasite. In addition, the praziquantel ED50 was 208.4 mg/kg against the adults of the 8th filial-generation S. japonicum without the selection pressure of praziquantel. Conclusions Compared with the experimentally induced praziquantel-resistant S. japonicum isolate, the adult worms of the filial-generation S. japonicum show a reduced sensitivity to praziquantel in the same host following infection with the mixture of cercariae of praziquantel-resistant and -sensitive S. japonicum isolates. The adult worms of the filial generation of the praziquantel-resistant S. japonicum isolate without the selection pressure of praziquantel may still maintain the resistance to praziquantel.