Modified Da-chai-hu Decoction (MDD), a traditional Chinese medicinal formulation, which was empirically generated from Da-chai-hu decoction, has been utilized to treat severe acute pancreatitis (SAP) for decades. The aim of the present study was to explore its potential organprotective mechanism in SAP. In the present study, rat SAP model was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, MDD (23.35 g/kg body weight, twelve times the clinical dose) were orally given at 2 h before and 10 h after injection. At 12 h after model induction, blood was taken from vena cava for analysis of amylase, diamine oxidase (DAO), pulmonary surfactant protein-A (SP-A), and C-reactive protein (CRP). Histopathological change of pancreas, ileum and lung was assayed by H&E staining, myeloperoxidase (MPO) activity were determinated using colorimetric assay, and the expressions of occludin and nuclear factor-κB (NF-κB) were detected by real-time RT-PCR and western blot, respectively. In addition, the tissue concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that in SAP rats, MDD significantly alleviated histopathological damage, depressed the MPO activity and the concentrations of TNF-α, IL-1β, and MCP-1 of pancreas, ileum and lung, and reduced the serum levels of amylase [(3283.4 ± 585.5) U·Lvs (5626.4 ± 795.1)U·L], DAO [(1100.1 ± 334.3) U·Lvs (1666.4 ± 525.3) U·L] and CRP [(7.6 ± 1.2) μg·mLvs (17.8 ± 3.8) μg·mL]. However, the serum SP-A concentration [(106.1 ± 16.6) pg·mLvs (90.1 ± 14.9) pg·mL] was elevated when treated SAP rats with MDD. Furthermore, MDD increased the occludin expression and reduced the NF-κB expression in pancreas, ileum and lung of SAP rats. Our findings suggested that MDD administration was an effective therapeutic approach for SAP treatment. It could up-regulate occludin expression to protect intercellular tight junction and down-regulate NF-κB expression to inhibit inflammatory reaction of pancreas, ileum and lung.

The dynamic accumulation rule of active substances in medicinal plants is of great value not only for medicinal material production and application,but also for the genetic mechanism study on the formation of medicinal ingredients,especially vital to guide medicinal material collection as well as experiment material selection and candidate gene screening in the analysis of biosynthesis pathway. This study investigated the accumulation of curcumins and terpenoids,and the biosynthesis of these metabolites,which are the active metabolites in Curcuma longa,a commonly used traditional Chinese medicine. Rhizoma of C. longa from leaf growing period,rhizome swelling period and dry matter accumulating period were used as experimental materials,to analyze the changes of metabolites and biosynthesis in the three periods by comparative transcriptome and metabolomes analysis.The results indicated that terpenoids accumulation and biosynthesis mainly occurred in leaf growing period,while curcumin accumulation and biosynthesis mainly occurred in dry matter accumulating period. Therefore,we suggested that turmeric rhizomes in leaf growth period were suitable for terpenoids biosynthetic pathway characterization,and rhizome in accumulation of dry matter period was suitable for curcuminoid biosynthesis pathway characterization. This study provides references for medicinal materialproduction and application,as well as biopathway analysis of active compounds for C. longa.
Curcuma ; chemistry ; Curcumin ; analysis ; Phytochemicals ; analysis ; Plants, Medicinal ; chemistry ; Rhizome ; chemistry ; Terpenes ; analysis

The solubility of nebivolol hydrochloride was determined in acidic aqueous media in the absence and presence of different concentration of NaCl, NaBr, or NaI at 37 ℃ in order to facilitate proper selection of dissolution media that have adequate discriminating power for enhancing the likelihood of a generic drug product to successfully pass in-vivo bioequivalence test. In the range of pH 5.0 to pH 1.0, the solubility of nebivolol hydrochloride decreased with the decrease in the pH of aqueous solution, and the solubility of nebivolol hydrochloride further decreased with the increase in the concentration of added sodium chloride. The solubility decrease of a few weakly basic drug molecules in acidic media and in higher concentration of added chloride was published previously by other researchers, and the observed decrease in the solubility in the presence of higher chloride concentration was interpreted in terms of common-ion effect. However, the results in this paper showed that the solubility of nebivolol hydrochloride also decreased when sodium chloride was replaced with sodium bromide or iodide. The approach described in this paper (i.e. substituting sodium chloride with sodium bromide or iodide) provides an effective method to verify whether common-ion effect is the true (or at least the sole) driving force behind the observed decrease in the solubility of nebivolol hydrochloride in the presence of sodium chloride. The solubility decrease reported in this paper can be interpreted in terms of salting-out effect of sodium chloride, bromide, and iodide. For hydrochloride salt of a weakly basic drug molecule like nebivolol hydrochloride, its solubility in an acidic dissolution medium can be purposely decreased to the lower end of sink condition by adding sodium chloride to make the resulting medium more discriminating. As shown in this paper, a medium at pH 1.2 with added sodium chloride is discriminating and this medium is shown to be bio-relevant to the in-vivo data collected under fasting condition (in-vivo study protocol was approved by Institutional Review Board).

Background: Extralevator abdominoperineal excision (ELAPE) has become a popular procedure for low rectal cancer as compared with abdominoperineal excision (APE). No definitive answer has been achieved whether one is superior to the other. This study aimed to evaluate the safety and efficacy of ELAPE for low rectal cancer with meta-analysis. Methods: The Web of Science, Cochrane Library, Embase, and PubMed databases before September 2019 were comprehensively searched to retrieve comparative trials of ELAPE and APE for low rectal cancer. Pooled analyses of the perioperative variables, surgical complications, and oncological variables were performed. Odds ratio (OR) and mean differences (MD) from each trial were pooled using random or fixed effects model depending on the heterogeneity of the included studies. A subgroup analysis or a sensitivity analysis was conducted to explore the potential source of heterogeneity when necessary. Results: This meta-analysis included 17 studies with 4049 patients, of whom 2248 (55.5%) underwent ELAPE and 1801 (44.5%) underwent APE. There were no statistical differences regarding the circumferential resection margin positivity (13.0% vs. 16.2%, OR = 0.69, 95% CI = 0.42-1.14, P = 0.15) and post-operative perineal wound complication rate (28.9% vs. 24.1%, OR = 1.21, 95% CI = 0.75-1.94, P= 0.43). The ELAPE was associated with lower rate of intraoperative perforation (6.6% vs. 11.3%, OR = 0.50, 95% CI = 0.39-0.64, P < 0.001) and local recurrence (8.8% vs. 20.5%, OR = 0.29, 95% CI = 0.21-0.41, P < 0.001) when compared with APE. Conclusions The ELAPE was associated with a reduction in the rate of intra-operative perforation and local recurrence, without any increase in the circumferential resection margin positivity and post-operative perineal wound complication rate when compared with APE in the surgical treatment of low rectal cancer.

Objective To study the physiological characteristics of Codonopsis Radix under drought stress; To reveal the physiological mechanism of Codonopsis Radix in response to drought stress. Methods Method of pot experiment was used to set up 4 water treatments: normal water supply, mild stress, moderate stress and severe stress. Through the determination of leaf relative water content, cell membrane permeability, osmotic adjustment contents and protective enzyme activity, the effects of drought stress on physiological characteristics of Codonopsis Radix were studied. Results With the drought stress increased, the chlorophyll a, total chlorophyll content and leaf relative water content of Codonopsis Radix decreased, but chlorophyll b had no obvious change; The conductivity increased first and then decreased; MDA contents increased first and then decreased and then increased; There was no significant change in the rate of superoxide anion production; POD and CAT activity increased; SOD had no significant change; The proline content increased first and then decreased; soluble sugar decreased; soluble protein had no significant change. Conclusion Under the condition of drought stress, by increasing the content of proline to regulate cell osmotic potential, Codonopsis Radixcan increase the antioxidant enzyme activity to reduce membrane lipid peroxidation damage to cells.

Background: Focal segmental glomerulosclerosis (FSGS) is a kidney disease that is commonly associated with proteinuria and the progressive loss of renal function, which is characterized by podocyte injury and the depletion and collapse of glomerular capillary segments. The pathogenesis of FSGS has not been completely elucidated; however, recent advances in molecular genetics have provided increasing evidence that podocyte structural and functional disruption is central to FSGS pathogenesis. Here, we identified a patient with FSGS and aimed to characterize the pathogenic gene and verify its mechanism. Methods: Using next-generation sequencing and Sanger sequencing, we screened the causative gene that was linked to FSGS in this study. The patient's total blood RNA was extracted to validate the messenger RNA (mRNA) expression of coenzyme Q monooxygenase 6 (COQ6) and validated it by immunohistochemistry. COQ6 knockdown in podocytes was performed in vitro with small interfering RNA, and then, F-actin was determined using immunofluorescence staining. Cell apoptosis was evaluated by flow cytometry, the expression of active caspase-3 was determined by Western blot, and mitochondrial function was detected by MitoSOX. Results: Using whole-exome sequencing and Sanger sequencing, we screened a new causative gene, COQ6, NM_182480: exon1: c.G41A: p.W14X. The mRNA expression of COQ6 in the proband showed decreased. Moreover, the expression of COQ6, which was validated by immunohistochemistry, also had the same change in the proband. Finally, we focused on the COQ6 gene to clarify the mechanism of podocyte injury. Flow cytometry showed significantly increased in apoptotic podocytes, and Western blotting showed increases in active caspase-3 in si-COQ6 podocytes. Meanwhile, reactive oxygen species (ROS) levels were increased and F-actin immunofluorescence was irregularly distributed in the si-COQ6 group. Conclusions This study reported a possible mechanism for FSGS and suggested that a new mutation in COQ6, which could cause respiratory chain defect, increase the generation of ROS, destroy the podocyte cytoskeleton, and induce apoptosis. It provides basic theoretical basis for the screening of FSGS in the future.
Adolescent ; Animals ; Apoptosis ; genetics ; physiology ; Cell Line ; Female ; Flow Cytometry ; Glomerulosclerosis, Focal Segmental ; genetics ; Humans ; Immunohistochemistry ; Mice ; Mutation ; genetics ; Podocytes ; metabolism ; pathology ; RNA, Messenger ; genetics ; RNA, Small Interfering ; genetics ; metabolism ; Ubiquinone ; analogs & derivatives ; genetics ; metabolism

Asian Continental Ancestry Group ; genetics ; China ; DNA (Cytosine-5-)-Methyltransferases ; genetics ; Humans ; Parkinson Disease ; genetics ; Polymorphism, Single Nucleotide

Objective To investigate the clinical therapeutic effect of mild hypothermia in elderly patients with severe traumatic brain injury.Methods 72 cases of elderly patients with severe traumatic brain injury(GCS ≤ 8) were divided into mild hypothermia therapy group(36 patients)and control group(36 patients) according to the random number table method.Mild hypothermia therapy group received mild hypothermia treatment while control group received normal treatment.The clinical prognosis was analyzed between the two groups.Results After 24h treatment,both mild hypothermia therapy group and control group intracranial pressure began to rise.But the intracranial pressure of the mild hypothermia therapy group(24 h:(13.0±4.5)mmHg,3 d:(16.6±4.0) mmHg,5 d:(19.9±3.9) mmHg,1 mmHg=0.133 kPa) were significantly lower than those of the control group (24 h:(16.6± 3.8) mmHg,3 d:(20.4±4.8) mmHg;5 d:(24.1 ± 6.2) mmHg),and the difference was statistically significant (t=2.225,2.260,2.192,P=0.035,0.033,0.039).The rate of good recovery to the control group and the mild hypothermia therapy group were 22.22％ and 47.22％ respectively while the mortality were 30.56％ and 13.89％ respectively,and the differences were statistically significant (x2 =4.936,5.675,P=0.047,0.035).Conclusion Mild hypothermia treatment can inhibit the increase of intracranial pressure and reduce disability rate and mortality in elderly patients with severe traumatic brain injury,which can increase the survival rate and improve the long-term prognosis.

OBJECTIVETo investigate the predictive value of preoperative detection of CEA and CA199 for prognosis in patients with stage II-III colorectal cancer (CRC).

METHODSClinicopathological and follow-up data of 266 patients with stage II-III colorectal cancer confirmed by pathology and undergoing radical resection in our department from 2004 to 2006 were retrospectively analyzed. The 5-year overall survival (OS) and disease-free survival (DFS) between normal CEA patients and increased CEA ones, and normal CA199 patients and increased CA199 ones were compared respectively. Moreover, the risk factors of OS and DFS were examined.

RESULTSAmong these 266 patients, 119 (44.7%) had preoperative elevated CEA, and 74 (27.8%) had increased CA199. The median follow-up time was 63 months. Kaplan-Meier survival curves indicated that patients with elevated preoperative CEA had worse 5-year OS (54.6% vs. 72.8%, P=0.001) and DFS (75.2% vs. 83.3%, P=0.042) than those with normal CEA respectively. Meanwhile, patients with elevated CA199 had worse OS (45.9% vs. 71.9%, P=0.000) and DFS (74.2% vs. 81.8%, P=0.047) than those with normal CA199 respectively. Multivariate analysis revealed that male (HR=3.016, 95% CI: 1.536-5.919, P=0.001), lymph node metastasis (HR=2.278, 95% CI: 1.272-4.081, P=0.006), and preoperative elevated CEA (HR=1.794, 95%CI: 1.022-3.149, P=0.042) were independent prognostic factors of DFS. While vascular thrombosis (HR=2.041, 95% CI: 1.294-3.221, P=0.002), lymph node metastasis (HR=2.480, 95% CI:1.548-3.972, P=0.000), and preoperative elevated CA199 (HR=2.145, 95% CI:1.414-3.254, P=0.000) were independent prognostic factors of OS in patients with stage II-III CRC.

CONCLUSIONCombined detection of preoperative CEA and CA199 can be used in evaluating the prognosis of patients with stage II-III CRC.

Antigens, Tumor-Associated, Carbohydrate ; blood ; Carcinoembryonic Antigen ; blood ; Colorectal Neoplasms ; diagnosis ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Multivariate Analysis ; Neoplasm Staging ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; Risk Factors ; Survival Rate

Objective:To investigate whether increased levels of preoperative carcinoembryonic antigen (CEA) and CA199 were associated with the mortality of patients with advanced colorectal cancer and to determine whether CA199 can be used to discriminate patients with normal preoperative CEA level from good to poor prognosis. Methods:A total of 314 patients with advanced colorectal cancer cases who underwent primary tumor resection were collected from 2014 to 2016 at Peking University Cancer Hospital and Institute. Preoperative CEA and CA199 serum levels were examined using electrochemiluminescence immunoassay. The association of CEA and CA199 with clinicopathologic features and their possible prognostic values were analyzed. Results:In the tested patients, 5.4%of whom had increased CA199 level but not up-regulated CEA level, whereas 28.3%only had increased CEA level, and 21.3%had both CEA and CA199 levels increased. Kaplan-Meier survival curves indicated that patients with elevated preoperative CEA level had worse disease-free survival (DFS) and overall survival (OS) than those with normal CEA (P<0.001 and P<0.001, respectively). Meanwhile, patients with elevated CA199 level had worse DFS and OS than those with normal CA199 (P<0.001 and P<0.001, respectively). Preoperative CA199 level could be used in discriminating patients with normal CEA from good to poor prognosis (P=0.012). Multivariate analysis revealed that elevated CA199 level was an independent prognostic factor for OS in patients with advanced colorectal cancer (HR=2.025, 95%CI=1.331-3.082, P=0.001). Conclusion:Combined detection of preoperative CEA and CA199 can be used in evaluating the prognosis of patients with advanced colorectal cancer. Preoperative serum CA199 level can be used in evaluating the prognosis of patients with colorectal cancer without an increase in CEA level. Patients with increased CA199 level had worse 5-year survival than those with increased CEA level.