4-Iodo-6-phenylpyrimidine (4-IPP) suppresses fibroblast-like synoviocyte- mediated inflammation and joint destruction associated with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic immune-mediated inflammatory disease that significantly impacts patients' quality of life. Fibroblast-like synovial cells (FLSs) within the synovial intima exhibit "tumor-like" properties such as increased proliferation, migration, and invasion. Activation of FLSs and secretion of pro-inflammation factors result in pannus formation and cartilage destruction. As an inhibitor of the cytokine, macrophage migration inhibitory factor (MIF), 4-Iodo-6-phenylpyrimidine (4-IPP) has been shown to reduce cell proliferation, migration, invasion, and the secretion of pro-inflammatory mediators in a variety of diseases. However, the usefulness of 4-IPP for RA treatment has not been assessed and was the purpose of this study. In vitro, 4-IPP was demonstrated to inhibit proliferation, migration, and invasion of RA FLSs, as well as the expression of pro-inflammatory cytokines. 4-IPP was also shown to inhibit MIF-induced phosphorylation of ERK, JNK, and p38, as well as reduce expression of COX2 and PGE2. In order to efficiently deliver 4-IPP to anatomical RA sites, we developed lactic-co-glycolic acid (PLGA) nanospheres, which not only protected 4-IPP from degradation but also controlled the release of 4-IPP. 4-IPP/PLGA nanospheres had potent anti-inflammatory activity and a high degree of biosafety. Results showed that local 4-IPP concentration was increased by nanosphere delivery, effectively reducing the inflammatory microenvironment as well as synovial inflammation, joint swelling, and cartilage destruction in a collagen-induced rheumatoid arthritis (CIA) rat model. Therefore, 4-IPP nanospheres are a sustained-release delivery system that may be an effective therapeutic strategy for RA treatment.

[Effectiveness analysis of proximal humerus internal locking system plate combined with rotator cuff reinforcement suture in treatment of Neer type â £ proximal humerus fracture].

Objective: To investigate the effectiveness of proximal humerus internal locking system (PHILOS) plate combined with rotator cuff reinforcement suture in the treatment of Neer type Ⅳ proximal humerus fracture. Methods: The clinical data of 48 patients with proximal humeral fractures admitted between January 2016 and December 2020 were retrospectively analyzed, including 18 males and 30 females. The age ranged from 28 to 69 years (mean, 56.3 years). The causes of injury included falling in 39 cases and traffic accident in 9 cases. The time from injury to operation was 2-5 days (mean, 2.8 days). All of them were Neer type Ⅳ proximal humerus fractures, including 11 patients with dislocation. All patients underwent internal fixation with a PHILOS plate after anatomical reduction of the greater nodule, and the rotator cuff was sutured to the plate to reinforce fixation. The operation time was recorded, the wound healing, fracture healing, and complications were observed. The visual analogue scale (VAS) score, Constant-Murley shoulder score, University of California Los Angeles (UCLA) score, and American Shoulder and Elbow Surgeons (ASES) score were used to evaluate shoulder function before operation, at 3 months after operation, and at last follow-up. Results: The operation time ranged from 65 to 90 minutes (mean, 76.9 minutes). All incisions healed by first intention. All patients were followed up 9-16 months (mean, 12 months). Fracture reduction was good and all fractures healed, the healing time was 2-6 months (mean, 4.6 months). There was no complication such as subacromial impingement, fracture redisplacement, and screw removal during follow-up. One patient had humeral head necrosis, but the basic function of the shoulder joint was acceptable, the symptoms were mild, and no treatment was performed. At 3 months after operation, the upper limb function of the patients basically recovered. The VAS score, Constant-Murley score, UCLA score, and ASES score significantly improved at 3 months after operation and at last follow-up when compared with preoperative, and further improved at last follow-up than at 3 months after operation ( P<0.05). Conclusion: PHILOS plate combined with rotator cuff reinforcement suture in the treatment of Neer type Ⅳ proximal humerus fracture has the advantages of promoting early postoperative rehabilitation exercise, improving postoperative function of shoulder joint, and reducing complications.

Effects of different frequencies of electro-acupuncture at shuigou (GV 26) on recovery of motor function in rats with focal cerebral ischemic injury.

OBJECTIVE: To investigate the effects of different frequencies of electro-acupuncture at Shuigou (GV 26) on the latent period and wave amplitude of motor evoked potentials (MEPs) in rats with focal cerebral infarction. METHODS: Fifty healthy male Wistar rats were randomly divided into five groups: controls, model, 2 Hz Shuigou, 50 Hz Shuigou and 100 Hz Shuigou. There were 10 rats in each group. Using a modification of a technique for middle cerebral artery occlusion, focal cerebral ischemic injury was induced in all rats except those in the control group. The rats in the control group received no treatment. After behavioral deficit had been evaluated using the Zausinger 6-point neurological function score, the rats in the Shuigou groups underwent acupuncture and continuous wave stimulation at a frequency of 2 Hz, 50 Hz or 100 Hz (intensity 1 mA) for 10 min twice daily for 3 days. The control and model groups underwent no intervention. Zausinger 6-point neurological function score and MEPs were measured 72 h after the start of treatment. RESULTS: The neurological function scores of the three Shuigou groups were significantly higher than those of the model group (P < 0.05). There was no significant difference between sides in the latency and amplitude of MEPs in the model group (P > 0.05). The latency on the affected side in the model group was significantly longer than that in the control group (P < 0.05) and the amplitude on affected side was significantly reduced (P < 0.01). After 3 days of electro-acupuncture, the latency on the affected side in the 2 Hz Shuigou group was significantly shortened (P < 0.05) and the amplitude was significantly increased (P < 0.05) compared with the model group. CONCLUSION: Low frequency electro-acupuncture at Shuigou (GV 26) can promote recovery of motor function after focal cerebral ischemic injury in rats.

[Effects of electro-acupuncture at Shuigou (DU26) point on motor evoked potential in rats with cerebral infarction].

OBJECTIVE: To investigate the effects of electro-acupuncture at Shuigou (DU26) on latency and amplitude of motor evoked potential (MEP) in rats after cerebral infarction. METHODS: Fifty healthy male Wistar rats were randomly divided into five groups as normal group, untreated group, sham-operated group, non-acupoint group and Shuigou group, with 10 rats in each group. By using a modification of the technique of middle cerebral artery occlusion, focal cerebral ischemia injury was induced in rats except normal and sham-operated groups. Rats in the normal group received no treatment. Rats in the sham-operated group underwent identical experimental procedures as the other groups, except that the nylon suture was inserted into the internal carotid artery. After the behavioral deficit was evaluated by using Zausinger 6-point neurological function score, rats in the Shuigou group and non-acupoint group were separately acupunctured and stimulated by continuous-wave with 2 Hz frequency, 1 mA intensity, for 10 minutes, twice a day for 3 days. Non-acupoint was located at the left side 0.5 cm of the Shuigou point. No intervention was given to the other groups. Zausinger 6-point neurological function and MEP were measured after 72-hour treatment. RESULTS: The latency at the affected side in the untreated group was significantly longer than that in the normal group (P<0.05), and the amplitude at the affected side was significantly reduced (P<0.01). After 3-day electro-acupuncture, the latency at the affected side of rats in the Shuigou group was obviously shortened as compared with the untreated group (P<0.05), and the amplitude was significantly increased (P<0.05). The latency at the affected side in the Shuigou group was shorter than that in the non-acupoint group (P<0.05), and the amplitude tended to increase as compared with the non-acupoint group, but there were no significant differences (P>0.05). There were no significant differences on the latency and amplitude between the untreated group and non-acupoint group (P>0.05). The neurobehavioral score of the Shuigou group was significantly higher than those of the untreated group and non-acupoint group (P<0.05), and there were no significant differences between the untreated group and non-acupoint group (P>0.05). CONCLUSION: Electro-acupuncture at Shuigou can increase the latency and amplitude of MEP in rats after cerebral infarction.