Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups

Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The anti liver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its "pharmacodynamic group". By searching the research on the anti hepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, β-elemene, can act on multi-target and multi-channel to play an anti hepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an anti hepatoma role. Network pharmacological analysis showed that the core targets of the "pharmacodynamic group" for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and "pharmacodynamic group", it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and "pharmacodynamic group" in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and "pharmacodynamic group".     

Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.     

Diagnosis of intrahepatic cholangiocarcinoma by Raman spectroscopy provides high efficiency: A protocol for systematic review and meta-analysis

Background:We aim to evaluate the efficiency of Raman spectroscopy (RS) in diagnosing suspected patients with intrahepatic cholangiocarcinoma (ICC), manifested by diagnostic sensitivity, specificity, and accuracy.Methods:We will research widely the articles concerning the use of RS in ICC through authenticated database including PubMed/Medline, EMBASE, Web of Science, Ovid, Web of Knowledge, Cochrane Library, and CNKI between January 2012 and November 2020, retrieving at least 1500 spectra with strict criteria. This study will be carried out in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We are going to summarize the test performance using random effects models.Results:Based on the pooled sensitivity, specificity, and diagnostic accuracy, we intend to provide the relative diagnostic efficiency in ICC through RS.Conclusion:Through this systematic review and meta-analysis, we intend to provide the pooled sensitivity, specificity and diagnostic accuracy of RS in the diagnosis of suspected ICC. Other parameters like positive likelihood ratios (LR), negative LR, diagnostic odds ratio (DOR), and area under curve (AUC) of the summary receiver operating characteristics (SROC) curve will also be calculated and related figures will be drawn to help illustrate the efficacy of RS in the diagnosis of ICC.     

Comparison between tension band and cerclage with X-Plate and lag screws in treatment of comminuted patellar fractures

BackgroundComminuted patellar fractures are not rare, and the ideal treatment method remains controversial. The present study was conducted to evaluate effects and compare complications of two different methods used to treat comminuted patellar fractures.MethodsFrom March 2010 to August 2016, 102 cases of 34-C2 or 34-C3 comminuted patellar fractures were treated at our hospital, wherein patients received two different treatments: titanium cable tension band with cerclage method (group A) and intrafragmentary screws with X-shaped plating technique (group B). At follow-ups, articular step-off, range of motion (ROM), Lysholm scores, time of union, and complications were recorded and analyzed. Radiographic and clinical data as well as rate of complications were statistically analyzed.ResultsIn total, 87 patients were included in the final analysis (n = 47 in group A and n = 40 in group B). No significant differences were noted in terms of cost of implant, age, gender, rate of 34-C3 fractures, rate of layered inferior pole fractures, postoperative articular step-off and union time. At 2-year follow-up, average Lysholm scores, ROM and rate of complications were (89.0 ± 4.5), (122°±12°) and (27.7%) in group A and (90.2 ± 3.9), (124°±11°) and (17.5%) in group B, respectively, with no significant differences (p > 0.05). The mean time of surgery in group B was shorter than that in group A with significant difference (p < 0.05).ConclusionsTreatment using the intrafragmentary screws and plate method for amenable comminuted patellar fractures achieved similar complication rate and favorable functional outcomes at the 2-year follow-up, which was comparable to the titanium cable tension band with cerclage method. Thus, the intrafragmentary screws and plate method is effective, safe and convenient for 34-C2/C3 comminuted patellar fractures, especially appropriate for patients with layered fragments.     

A Phase I Dose Escalation Study of the Safety,Tolerability, and Pharmacokinetics of Ipilimumab in Chinese Patients with Select Advanced Solid Tumors

Lessons Learned

• The overall safety profiles of ipilimumab 3 mg/kg and 10 mg/kg administered every 3 weeks, were consistent between Chinese patients with solid tumors in the current study and patients from previous U.S. ipilimumab monotherapy studies. No new safety signals were identified.
• The mean systemic exposures to ipilimumab (assessed by first dose area under the curve during the dosing interval and maximum serum concentration) were numerically lower in the Chinese patient population than in U.S. patients for both 3 mg/kg and 10 mg/kg doses; however, the range of serum concentrations in the Chinese and U.S. populations overlapped (3 mg/kg and 10 mg/kg), suggesting that ipilimumab pharmacokinetics was ethnically insensitive in this study.

BackgroundThis phase I, open‐label study assessed ipilimumab safety, tolerability, pharmacokinetics (PK), immunogenicity, and antitumor activity in Chinese patients with unresectable, metastatic, recurrent malignant melanoma (MM) or nasopharyngeal carcinoma (NPC).MethodsOf 39 patients enrolled, 25 received ipilimumab (11 patients received 3 mg/kg, and 14 patients received 10 mg/kg). Reasons for not receiving treatment were withdrawal of consent (3 patients), no longer meeting the criteria (10 patients), and one recorded as “other.” During the induction phase, patients received ipilimumab (3 mg/kg, i.v.), on day 1 of a 3‐week cycle, to a maximum of four doses or progressive disease (PD). During the maintenance phase at week 24, patients received ipilimumab (3 mg/kg, i.v.) on day 1 of a 12‐week cycle, to a maximum of 3 years or PD. Considering the co‐primary safety and PK endpoints, the successive dosing required nine patients with two or fewer dose‐limiting toxicities during the 42‐day observation period to proceed with a new cohort of nine patients at 10 mg/kg.ResultsIpilimumab safety and PK profiles were similar in Chinese and predominantly White populations. Ipilimumab was well tolerated. Most adverse events (AEs) were grades 1–2 and experienced by 11 patients treated with 3 mg/kg and 14 patients treated with 10 mg/kg. There were no new safety concerns. Incidence of anti‐ipilimumab antibodies was low (1 of 10 in the 3 mg/kg patients and 2 of 13 in the 10 mg/kg patients) and without safety implications. In the 3 mg/kg group, 8 of 11 patients had PD. In the 10 mg/kg group (all NPC, 0 MM patients), 11 of 14 patients had PD. Three patients had stable disease (one at 3 mg/kg and two at 10 mg/kg).ConclusionIpilimumab was well tolerated in Chinese patients, showing similar safety and PK to previous studies in predominantly White populations.     

Collimating micro-lens fiber array for noncontact near-infrared diffuse correlation tomography

Near-infrared diffuse correlation spectroscopy/tomography (DCS/DCT) has recently emerged as a noninvasive measurement/imaging technology for tissue blood flow. In DCT studies, the high-dense collection of light temporal autocorrelation curves (g₂(τ)) via fiber array are critical for image reconstruction of blood flow. Previously, the camera-based fiber array limits the field of view (FOV), precluding its applications on large-size human tissues. The line-shape fiber probe based on lens combination, which is predominantly used in current DCT studies, requires rotated-scanning over the surface of target tissue, substantially prolonging the measurement time and increasing the system instability. In this study, we design a noncontact optical probe for DCT based on collimating micro-lens fiber array, termed as FA-nc-DCT system. For each source/detector fiber, a single optical path was collimated by coupling with one micro-lens in the fiber array that is integrated in a square-shape base. Additionally, an 8×8 optical switch is used to share the hardware laser and detectors without spatial scanning. The FA-nc approach for the precise collection of g₂(τ) curves was validated through a speed-varied phantom experiment and the human experiments of cuff occlusion, from which the expected value of the blood flow index (BFI) was obtained. Furthermore, the flow anomaly in the phantom and the ischemic muscle in human were accurately reconstructed from the FA-nc-DCT system, which is combined with the imaging framework based on the Nth-order linear algorithm that we recently created. Those outcomes demonstrated the great potential of FA-nc-DCT technology for fast and robust imaging of various diseases such as human breast cancers.     

经皮椎体成形术导致巨大腹膜后血肿成功救治1例报道

经皮椎体成形术是一种安全有效的微创手术,腹膜后血肿是其罕见但严重的并发症。我们报告一例经皮椎体成形术RH阴性(熊猫血)患者术后并发巨大腹膜后血肿,经保守和输血等支持治疗,病人康复出院。脊柱医生应了解这种罕见但潜在致命的并发症,因为早期认识和及时预防是降低其发病率的基础。