B7 Induces Apoptosis in Colorectal Cancer Cells by Regulating the Expression of Caspase-3 and Inhibits Autophagy.

Purpose: Heterocyclic compounds are organic compounds with heterocyclic structures, which are common in drug molecules. They include pyrazines with diverse functions, including anti-cancer, antimicrobial, antidiabetic, and anticholinergic activities. In this study a new small molecular compound B7 based on tetrazolium substituted pyrazine was synthesized and its effect on the progression of colorectal cancer (CRC) and its potential mechanism were investigated. Methods: We synthesized a series of tetrazolium-substituted pyrazine compounds by chemoenzymatic method. NCM460 (Human), HCT116 (Human), SW480 (Human) cell lines were selected to analyse the inhibitory effect of B7 on CRC by CCK-8, apoptosis, cell migration and invasion, qPCR, Western blotting, molecular docking, immunofluorescence. Moreover, a CRC xenograft model of mice was used to analyzed the role of B7 in vivo. Results: Among these compounds, 3-methyl-5je-6-bis (1H-tetrazole-5-yl) pyrazine-2-carboxylic acid (B7) inhibited CRC cell proliferation and induced apoptosis. The expression of Caspase-3 was increased after B7 treatment. In addition, the mitochondria abnormalities was observed in B7 group due to decrease the expression of Beclin-1. In addition, B7 inhibited the migration and invasion in CRC cells. Finally, the results showed that B7 had anti-tumor activity in CRC xenograft model of mice. Conclusion: In summary, compound B7 was synthesized efficiently using tetrazolium-substituted pyrazine via a chemoenzymatic method. Moreover, B7 have ability to regulate the expression of Caspase-3 which induced apoptosis in CRC cells. In addition, decreased Beclin-1 expression after B7 treatment, indicating inhibited autophagy. This study showed that B7 effectively induced apoptosis and inhibited autophagy in CRC cells.

Reverse Shoulder Arthroplasty in Patients with Rheumatoid Arthritis: Early Outcomes, Pitfalls, and Challenges.

OBJECTIVE: To evaluate the early outcomes and risk factors of reverse shoulder arthroplasty (RSA) in patients with rheumatoid arthritis (RA). METHODS: A retrospective study was performed on RA patients who had undergone RSA between January 2016 and January 2018. Preoperative glenohumeral joint damage was evaluated according to two radiographic classification systems. The severity of joint damage was estimated using Larsen's method, while the Levigne-Franceschi method was used to assess the type of destruction. Further, we recorded intra- and postoperative complications. Visual Analogue Scale (VAS) was used to assess the degree of shoulder pain while shoulder function was evaluated with the American Shoulder and Elbow Surgeons (ASES) Shoulder Score. In addition, patients' subjective outcome and range of shoulder motion were recorded. Radiographs were taken and examined during the follow-up period. Paired t-test was used to determine the difference in measurement data between preoperative and the last follow-up. VAS was analyzed using the Wilcoxon matched-pairs signed-rank test. RESULTS: A total of 14 patients with 14 shoulders were included. All the patients were female with an average age of 60.29 years (range, 49-71 years) at the time of surgery and an average RA disease duration of 24.57 years (range, 5-40 years). Seven of the 14 patients had a history of joint surgery related to RA. Meanwhile, 11 of the 14 shoulders showed glenoid bone defect, and eccentric reaming was performed intraoperatively to avoid base plate malposition. The mean follow-up period for the 14 patients was 2.76 years (range, 2-4 years). The mean VAS decreased from a value of 5.71 ± 1.10 preoperatively to 1.36 ± 0.61 postoperatively (P < 0.001). On the contrary, the ASES score showed an increase from 33.93 ± 6.89 to 76.67 ± 5.23 (P < 0.001). An increase in active forward elevation, abduction, and external rotation with the arm in 90° of abduction from 85.71° ± 17.61°, 77.14° ± 19.43°, and 17.14° ± 10.97° to 126.43° ± 5.23°, 106.42° ± 11.72°, and 38.57° ± 14.57°, respectively, was observed (P < 0.001). Subjective outcome assessment showed that 13 of the 14 patients were very satisfied or satisfied with the operation, while one patient was uncertain due to co-existing ipsilateral elbow lesion. Notably, one patient acquired a humeral periprosthetic fracture during the operation. In this study, no major complications such as periprosthetic joint infection and dislocation or implant loosening were observed. Further, no patients underwent revision for any reason at the end of the follow-up. CONCLUSIONS: RSA could achieve good early outcomes without high complication rates in patients with RA. Glenoid bone defects and adjacent joints involvement were common in this patient group, which might increase the risk of surgery and affect postoperative satisfaction.

Efficacy of different-frequency TEAS on acute pain after the total knee arthroplasty: a study protocol for a parallel group randomized trial.

BACKGROUND: Total knee arthroplasty (TKA) is an optimal option for patients with middle-to-end-stage knee osteoarthritis. However, the management of postoperative acute pain remains inefficient. Transcutaneous electrical acupoint stimulation (TEAS) is a nonpharmacological method to manage postoperative acute pain. Different frequencies of TEAS have been tested using varying parameters, but the optimal analgesic frequency remains controversial. The aim of this study was to explore the optimal analgesic frequency of TEAS for treating acute pain after the primary unilateral TKA. METHODS/DESIGN: This is a double-blind, randomized controlled trial. A total of 156 patients are randomly assigned to: G1, 5 Hz TEAS; G2, 100 Hz TEAS; G3, mixed TEAS (alternative use of daily 5 Hz and 100 Hz TEAS) and G4, placebo TEAS. In the G1, G2 and G3 groups, TEAS is conducted at acupoints SP9 and GB34 of the leg that was operated on (at a wave of continuous, balanced and asymmetrical biphasic square, with a pulse width of 200 µs, and a strong but comfortable current) for 30 min prior to a 30-min rehabilitation session per day for 2 weeks. In G4 group, TEAS is delivered at a strong but comfortable current for 30 s, then the current is gradually decreased to none over the next 15 s. The primary outcomes are measured before surgery, at baseline (POD 3, before TEAS intervention), week 1 and 2 after TEAS intervention with the Numeric Pain Rating Scale and The American Knee Society Score. The secondary outcomes include: (1) Active range of motion of the knee that was operated on; (2) Surface electromyography of both quadriceps; (3) Modified 30-s sit to stand test; (4) Additional usage of analgesia; and (5) SF-36. The additional outcomes include: (1) Patients' satisfaction rate; (2) Patient's expectation rate; and (3) Incidence of analgesia-related side effects. To test the blinding of participants and assessors, they are asked to guess whether the subjects received active or placebo TEAS within 5 min after the latest intervention. The safety and financial cost of TEAS are assessed. DISCUSSION: Mixed TEAS has more favorable effect on acute pain control than the placebo or 5 Hz or 100 Hz TEAS. TRIAL REGISTRATION: ChiCTR1800016347 . Date of registration was 26 May 2018. Retrospectively registered.

[Clinical result of forefoot correction by the first ray stabilization combined with resection of the lesser metatarsal head procedure for patient with rheumatoid arthritis].

OBJECTIVE: To introduce the procedure of the 1st ray stabilization combined with resection of the lesser metatarsal heads for patient with severe forefoot deformity caused by rheumatoid arthritis (RA) and evaluate the short to mid-term clinical results. METHODS: From Oct. 2006 to Aug. 2010,97 patients (129 feet) aged from 36 to 67 years (average 54), with forefoot deformity caused by rheumatoid arthritis were reviwed. There were 88 males and 9 females,65 single lateral involved and 32 bilateral involved, the average duration of disease was 17 years (6 to 32 years). The 1st ray instability and lesser metatarsophalangeal (MTP) joint stiff dislocation were found in all cases. The first ray stabilization combined with resection of the lesser metatarsal head procedure were performed for all cases. The radiographic Hallux valgus angle (HVA) and intermetatarsal angle (IMA) were measurde and the JSSF (Japanese Society for Surgery of the Foot) score were evaluated before operation and every follow up. RESULTS: The average followed-up was 37 months (6 to 52 months) for all patients except 5 (7 feet) and 1 died for acute cardiac infarction 1 year after operation. The average JSSF score improved from (33.2 +/- 8.2) points preoperative to (67.3 +/- 3.1) points at final followed-up (P < 0.01); the average HVA was corrected from (50.0 +/- 11.8) degrees preoperative to (21.2 +/- 3.2) degrees at final follow up (P < 0.01); the average IMA was corrected from (15.5 +/- 3.6) degrees preoperative to (9.7 +/- 6.6) degrees at final follow up (P < 0.01). MTP joint nonunion was found in 4 feet. A radiographic high density mass was found in the 1st cuneiform bone during 8 to 11 months followed-up in 3 feet; delayed wound healing was happened in 9 feet; MTP joint infection was happened in 2 feet; tarsometatarsal joint infection was happened in 1 foot; lesser MTP joints deformity recurrence were found in 16 feet. CONCLUSION: The characters of forefoot with RA in later stage are the 1st ray deformity and instability compound with the lesser toes deformity. The 1st ray stability procedure which include the 1st MTP arthrodesis and the Lapidus procedure can correct the 1st ray deformities and rebuilt its stability. The lesser toes metatarsal head resection is effective in correct their deformity. This combined procedure is reliable. It is suitable for patients with severe Hallux valgus, increased IMA, tarsometatarsal joint instability and the lesser MTP joint stiff dislocation.

A nonfatal case and 2 fatal cases of paraneoplastic pemphigus: can a complement indirect immunofluorescent test help to identify fatal "group A" paraneoplastic pemphigus cases?

We studied 3 recent cases of paraneoplastic pemphigus (PNP) in detail. Two patients died despite concerted management efforts. One patient received no treatment after the appearance of PNP and recovered completely from both PNP and lymphoma. Multiple serum studies of these 3 patients plus 9 other proven PNP cases revealed that 8 of 9 fatal PNP cases (referred to here as "group A") had distinctive cell surface antibodies detected by complement indirect immunofluorescent (CIIF) tests on monkey esophagus sections. By contrast, none of the sera from 3 patients with PNP who experienced long-term survival (referred to here as "group B") and none of 20 pemphigus vulgaris or 10 pemphigus foliaceus control sera revealed similar beaded cell surface CIIF reaction patterns, a difference that is statistically significant (P <.0001). Cell surface CIIF reaction patterns of group A PNP antibodies resemble the pattern of pemphigus antibody reactions in indirect immunofluorescent tests on the same substrate; however, the latter tend to be thinner and more linear, whereas the cell surface CIIF pattern tends to be more beaded, suggesting possible desmosomal reactions. We believe this test is useful in identifying an aggressive group A form of PNP.