Two new meroterpenoids from the bark of Cinnamomum cassia and their antioxidant activity.

Two new (1 and 2) meroterpenoids were isolated from the bark of Cinnamomum cassia. Their structures were determined by spectroscopic analyses and chemical methods. Antioxidant activities of 1 and 2 were evaluated by the ORAC and DPPH radical scavenging assays, and the results revealed that compound 2 displayed oxygen radical absorbance capacity. The discovery of compounds 1 and 2 added new members of this kind of natural product.

[Network Meta-analysis of Chinese medicine injections in treatment of rheumatoid arthritis].

This study aims to systematically evaluate the efficacy and safety of Chinese medicine injections in the treatment of rheumatoid arthritis. Specifically, randomized controlled trial(RCT) in the treatment of rheumatoid arthritis with Chinese medicine injections was retrieved from PubMed, EMbase, Cochrane Library, Web of Science, Wanfang, CNKI, VIP, and SinoMed(from inception to February 16, 2022). RevMan 5.3 and Stata 15.0 were employed for data analysis. Finally, 53 RCTs, involving 4 280 patients were included. The experimental groups involved the following injections: including Danshen Chuanxiongqin Injection, Tanshinone Ⅱ_A Sodium Sulfonate Injection, Danhong Injection, Dengzhan Xixin Injection, Gugua Extract Injection, Honghua Injection, Lugua Polypeptide Injection, Lugua Polypeptide Injection + Tanshinone Ⅱ_A Sodium Sulfonate Injection, Shuxuetong Injection, Zhengqing Fengtongning Injection, Compound Danshen Injection, and Xuebijing Injection. The network Meta-analysis showcased the following trends.(1) As for improving total clinical effective rate, the surface under the cumulative ranking curve(SUCRA) followed the order of conventional treatment of western medicine combined with Xuebijing Injection > combined with Gugua Extract Injection > combined with Compound Danshen Injection > combined with Danshen Chuanxiongqin Injection > combined with Honghua Injection > combined with Zhengqing Fengtongning Injection > combined with Danhong Injection > combined with Lugua Polypeptide Injection > combined with Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Dengzhan Xixin Injection.(2) As for improving erythrocyte sedimentation rate(ESR), SUCRA followed the order of conventional treatment of western medicine combined with Xuebijing Injection > combined with Shuxuetong Injection > combined with Honghua Injection > combined with Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Gugua Extract Injection > combined with Danhong Injection > combined with Lugua Polypeptide Injection > combined with Dengzhan Xixin Injection > combined with Lugua Polypeptide Injection + Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Danshen Chuanxiongqin Injection > combined with Zhengqing Fengtongning Injection.(3) As for improving rheumatoid factor(RF), SUCRA followed the order of conventional treatment of western medicine combined with Lugua Polypeptide Injection > combined with Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Lugua Polypeptide Injection + Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Gugua Extract Injection > combined with Danshen Chuanxiongqin Injection > combined with Zhengqing Fengtongning Injection > combined with Danhong Injection > combined with Dengzhan Xixin Injection.(4) As for improving C-reactive protein(CRP), SUCRA followed the order of conventional treatment of western medicine combined with Xuebijing Injection > combined with Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Lugua Polypeptide Injection + Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Honghua Injection > combined with Danshen Chuanxiongqin Injection > combined with Dengzhan Xixin Injection > combined with Gugua Extract Injection > combined with Lugua Polypeptide Injection > combined with Zhengqing Fengtongning Injection > combined with Danhong Injection.(5) As for alleviating morning stiffness, SUCRA followed the order of conventional treatment of western medicine combined with Shuxuetong Injection > combined with Lugua Polypeptide Injection > combined with Dengzhan Xixin Injection > combined with Xuebijing Injection > combined with Gugua Extract Injection > combined with Zhengqing Fengtongning Injection > combined with Danhong Injection > combined with Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Honghua Injection.(6) As for improving disease activity score(DAS28), SUCRA followed the order of conventional treatment of western medicine combined with Lugua Polypeptide Injection + Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Lugua Polypeptide Injection > combined with Zhengqing Fengtongning Injection > combined with Honghua Injection > combined with Gugua Extract Injection > combined with Dengzhan Xixin Injection. The experimental groups had lower incidence of adverse reactions than the control group. The results of network Meta-analysis suggest that on the combination of conventional treatment of western medicine with Chinese medicine injections can improve the efficacy on rheumatoid arthritis. However, in view of the great differences in the quality and number of studies included for different therapies, the SUCRA of Chinese medicine injections need to be further verified with high-quality multi-center, large-sample, randomized double-blind trials.

Quantitative susceptibility-weighted imaging in amyotrophic lateral sclerosis with 3.0 T magnetic resonance imaging.

OBJECTIVE: To evaluate alterations in phase-shift values in the gray matter of patients with amyotrophic lateral sclerosis (ALS) using susceptibility-weighted imaging (SWI). METHODS: Twenty patients with definite or probable ALS and 19 age- and sex-matched healthy controls were enrolled. SWI was performed using a 3.0 T magnetic resonance imaging scanner. Phase-shift values were measured in corrected phase images using regions of interest, which were placed on the bilateral precentral gyrus, frontal cortex, caudate nucleus, globus pallidus, and putamen. RESULTS: Phase-shift values of the precentral gyrus were significantly lower in ALS patients (-0.176 ± 0.050) than in the control group (-0.119 ± 0.016) on SWI. The average phase-shift values of the frontal cortex, caudate nucleus, globus pallidus, and putamen in ALS patients (-0.089 ± 0.023, -0.065 ± 0.016, -0.336 ± 0.191, and -0.227 ± 0.101, respectively) were not significantly different from those in the healthy controls (-0.885 ± 0.015, -0.079 ± 0.018, -0.329 ± 0.136, and -0.229 ± 0.083, respectively). CONCLUSIONS: Compared with healthy controls, ALS patients had a lower phase-shift value in the precentral gyrus, which may be related to abnormal iron overload. Thus, SWI is a potential method for identifying ALS patients.

Curcumin-Activated Mesenchymal Stem Cells Derived from Human Umbilical Cord and Their Effects on MPTP-Mouse Model of Parkinson's Disease: A New Biological Therapy for Parkinson's Disease.

BACKGROUND: The aim of this study was to investigate the effects of human umbilical cord mesenchymal stem cell activated by curcumin (hUC-MSCs-CUR) on Parkinson's disease (PD). hUC-MSCs can differentiate into many types of adult tissue cells including dopaminergic (DA) neurons. CUR could protect DA neurons from apoptosis induced by 6-hydroxydopamine (6-OHDA). Therefore, we used the hUC-MSCs activated by CUR for the treatment of PD in an animal model. METHODS: The hUC-MSCs-CUR was transplanted into the MPTP-induced PD mouse models via the tail vein. We found that hUC-MSCs-CUR significantly improved the motor ability, increased the tyrosine hydroxylase (TH), dopamine (DA), and Bcl-2 levels, and reduced nitric oxide synthase, Bax, and cleaved caspase 3 expression in PD mice. The supernatant of hUC-MSCs-CUR (CM-CUR) was used to stimulate the SH-SY5Y cellular model of PD; cell proliferation, differentiation, TH, and neuronal-specific marker microtubular-associated protein 2 (MAP2) expressions were examined. RESULTS: Our data showed that CM-CUR significantly promoted cell proliferation and gradually increased TH and MAP2 expression in SH-SY5Y PD cells. The beneficial effects could be associated with significant increase of rough endoplasmic reticulum in the hUC-MSCs-CUR, which secretes many cytokines and growth factors beneficial for PD treatment. CONCLUSIONS: Transplantation of hUC-MSCs-CUR could show promise for improving the motor recovery of PD.

Brain activation patterns during unilateral premolar occlusion.

OBJECTIVE: To observe the characteristics of brain activation during unilateral premolar occlusion. METHODS: Functional magnetic resonance imaging was collected from 10 healthy volunteers during occlusion of the left first premolar (L1), left second premolar (L2), and right first premolar (R1). The brain activation patterns were analyzed, and the primary sensorimotor cortex, supplementary motor area, insula, thalamus, and prefrontal cortex were chosen as regions of interest. RESULTS: Single premolar occlusion activated the precentral gyrus, postcentral gyrus, cerebellum, thalamus, frontal lobe, hippocampus, cingulate gyrus, and parietal lobe. The brain areas showing activation during single premolar occlusion were similar to those activated by chewing. The activation pattern of L1 was more similar to that of L2 than R1. No significant left and right hemisphere differences in signal intensity were detected within the regions of interest. CONCLUSION: Brain activation patterns from two ipsilateral premolars were more similar than the pattern from a contralateral premolar.

The effect of Astragaloside IV on immune function of regulatory T cell mediated by high mobility group box 1 protein in vitro.

High mobility group box 1 protein (HMGB1), a potent pro-inflammatory cytokine, contributes to the pathogenesis of diverse inflammatory and infectious disorders. Some studies have illustrated the potential effect of HMGB1 on regulatory T cells (Tregs). Astragaloside IV (AST IV) isolated from a Chinese herb, Astragalus mongholicus, is known to have a variety of immunomodulatory activities. However, it is not yet clear whether AST IV possesses potential regulatory effect on the pro-inflammatory ability of HMGB1 with subsequent activation of Tregs. This study was carried out to investigate the antagonistic effects of different doses of AST IV on the immune function of Tregs mediated by HMGB1 in vitro. Tregs isolated from the spleens of mice were co-cultured with HMGB1 and/or AST IV. Cell phenotypes of Tregs were analyzed, and the contents of various cytokines in the cell supernatants as a result of co-culture and the proliferation of CD4(+)CD25(-) T cells were determined. Results showed that HMGB1 stimulation resulted in significantly down-regulation of expressions of Tregs cell phenotypes. However, AST IV can rival the suppressing effect of HMGB1 on immune function of Tregs with a dose-dependent in vitro. These results indicate that AST IV has the potential therapeutic action on inflammation augmented by HMGB1.

[Efficacy analysis of THP-containing regimens as neoadjuvant and adjuvant chemotherapy for primary breast cancer].

OBJECTIVE: To evaluate the effect of anthracycline pirarubicin-based regimen in association with different ways of fluorouracil (5-Fu) as neoadjuvant and adjuvant chemotherapy for primary breast cancer. METHODS: Two hundred and eighty-nine primary breast cancer patients who were to be operated, two to eight cycles of pirarubicin in association with cyclophosphamide and 5-Fu (CTF or CTFci regimen) were given before operation. The pathological response rate, effect and its relation with the infusion routes of 5-Fu were analyzed. RESULTS: The overall pathological complete remission (pCR) rate was 28.4%. The median follow-up period was 39 months. The 5-year DFS was 87.6% (95% CI:82.1% to 92.7%), 5-year DDFS was 89.9% (95% CI:84.0% to 95.8%), and overall survival was 99.6%. CTFci (5-Fu, continuous infusion) regimen was superior to CTF regimen in pCR rates (32.3% vs. 20.2%, P = 0.037), and 5-year DDFS were 92.9% and 80.1%, respectively (P = 0.015). The pCR group was superior to non-pCR group in 5-year DDFS (92.4% vs. 85.6%, P = 0. 033). The pCR rate of patients with ER/PR-positive tumor was significantly lower than those of ER/PR-negative (P = 0.004). The 5-year DDFS rates of HER-2 (+) and HER-2(-) groups were 75.0% and 91.9%, respectively (P = 0.043). In the ER/PR-positve group, the 5-year DDFS of CTFci regimen was superior to those of CTF regimen, 91.4% vs. 81.4% (P = 0.047). CONCLUSIONS: CTF/CTFci regimen as neoadjuvant and adjuvant chemotherapy is effective for primary breast cancer. CTFci regimen is superior to CTF regimen in pathological complete response rate and 5-year DDFS. CTFci regimen may do better to ER/PR (+) patients' benefits compared with CTF regimen.

Weekly paclitaxel improved pathologic response of primary chemotherapy compared with standard 3 weeks schedule in primary breast cancer.

The purpose of this study is to compare the efficacy of weekly paclitaxel to every-3-week schedule in terms of pathologic response and toxicity which caused treatment delay in primary chemotherapy of breast cancer. After pretreatment of two cycles of cyclophosphamide/ pirarubicin/ fluorouracil (cyclophosphamide 500 mg/m(2) days 1, 8; pirarubicin 35 mg/m(2) days 1, 8; 5-Fu 200 mg/m(2) day ci day 1-28, every 4 weeks), 219 women with histologically confirmed T(1-3) N(0-2) M(0) invasive breast cancer, whose vertical diameters production of breast tumor reduced not more than 75%, were randomized to receive four cycles of Pq3wC (arm A: paclitaxel 175 mg/m(2) day 1, carboplatin AUC 6 d1, every 3 weeks) or Pq1wC (arm B: paclitaxel 60 mg/m(2) days 1, 8, 15, carboplatin AUC 6 day 1 for every 3 weeks) before surgery, stratified by partial or no response (stable disease and progression of disease) evaluated by ultrasonography. Pathologic response of the primary tumor was assessed by using Miller and Payne grading system. We defined grade 4/5 as excellent response, grade 3/4/5 as response and treatment delay as paclitaxel administration being delayed at least 1 week because of toxicity in this study. 213 patients (2 cases with concurrent bilateral breast cancer) were eligible for analysis, 109 patients with 110 lesions in arm A and 104 patients with 105 lesions in arm B. Patients in arm B had a higher excellent pathologic response rate and a higher pathologic response rate compared with patients in arm A (59.0 vs. 45.5%, P = 0.046 and 86.7 vs. 71.8%, P = 0.007). Pathologic complete response (pCR) rate in breast alone was similar between two arms (P = 0.733), but there was a higher pCR rate in patients with partial response to two cycles of cyclophosphamide/pirarubicin/fluorouracil than those with no response (32.4 vs. 13.9%, P = 0.001). There was no treatment-related death, however more patients in arm B than in arm A experienced treatment delay caused by toxicity (60.6 vs. 11.9%, P < 0.001). Under the condition of same cumulative doses, weekly paclitaxel was more effective than 3 weeks schedule in terms of pathologic response to primary chemotherapy in breast cancer, and caused more treatment delay related to toxicity though well tolerant.

[The application of conservative surgery for local advanced and bigger primary breast carcinoma].

OBJECTIVE: To discuss the application of conservative surgery for local advanced and bigger primary breast carcinoma (> 4 cm in diameter). METHODS: Thirty-three primary breast cancer patients with tumor diameter more than four centimeters were treated with wide local excision and axillary lymph node dissection. Before operation, neoadjuvant chemotherapy with anthracyclines based combined regimen was done in thirty-one patients. RESULTS: Thirty-one patients received one to eight cycles of neoadjuvant chemotherapy (mean 3.7 cycles). The response rate was 100%, including clinical complete remission in 19 cases, clinical partial remission in 12 cases and pathological complete remission in 9 cases. The final margin negative rate was 100% in thirty-three patients and first margin negative rate was 75.8% during operation. After a median follow-up of 27 months (range 2-39 months), up to date yet, no relapse case was found. The relapse-free survival was 100%. CONCLUSIONS: Combining with neoadjuvant chemotherapy, breast-conserving therapy can be done successfully for most primary breast cancer patients with local advanced and bigger tumor. The curative effect was the same as the patient with smaller tumor in a short term follow-up.

[Neoadjuvant chemotherapy for primary breast cancer].

OBJECTIVE: To evaluate the feasibility and effect of fluorouracil (5-Fu) in association with anthracycline-based regimen as neoadjuvant chemotherapy for primary breast cancer. METHODS: For one hundred and eleven primary breast cancer patients with 114 lesions who were to be operated, two to six cycles of 5-Fu (continuous infusion) in association with epirubicin or pirarubicin and cyclophosphamide (CEFci or CTFci regimen) were given before operation. The response rate, side effect and its relation with tumor characteristics were studied. RESULTS: The overall response rate was 87.7%, of which the complete clinical response was 39.5%, pathological complete response was 23.7%, only one patient (0.9%) showed progressive disease. The regimen containing pirarubicin was superior to epirubicin regimen in pathological complete response rate (P < 0.05). Alopecia was mild in pirarubicin regimen as compared with epirubicin regimen but neutropenia was more severe in pirarubicin regimen than that in epirubicin regimen. Hormonal receptor expressions were significantly related to treatment response, the pathological complete response rate was 33.3% in oestrogen or progestin receptor negative tumors, but it was 7.5% in the positive tumors (P < 0.005). No correlation was observed between treatment response and tumor size, as well as HER-2 expression. CONCLUSION: CTFci/CEFci regimen as neoadjuvant chemotherapy is effective and safe for primary breast cancer. CTFci regimen is superior to CEFci regimen in response rate. The patients with negative hormonal receptor are more sensitive to the neoadjuvant chemotherapy.