Large number of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations are responsible for a wide spectrum of disease expressions in CF (cystic fibrosis). They includs not only the malfunction of the lung and pancreas, intestinal obstruction, and incapable of salt reabsorption, but also some kinds of male infertility, such as congenital bilateral absence of the vas deferens (CBAVD),poor sperm quality, the obstruction and agenesis of the epididymis. More recent studies have indicated that CFTR gene mutations have a far-reaching effect on human reproduction.

The abnormality of the central noradrenergic system in Alzheimer's disease has two cases: decrease or increase. The former is easy to be understood, because it is resulted from the outstanding forfeit of the noradrenergic neurons in the nucleus locus ceruleus (nLC); but the noradrenalin concentration does not change and enen increase, it seems to disagree with the loss of the noradrenergic neurons in the nLC. This article put emphasis on it, enumerated the related evidence and analyzed the possible causes. At present time, the drugs to increase noradrenalin is used mostly in clinic. This paper summarized it and put forth our own opinions.

AIM:To explore the roles of brain-stem auditory evoked potential(BAEP) in early monitoring the hearing loss and brain damages in hyperbilirubinemia and nitric oxide(NO) in the pathogenesis of bilirubin-induced hearing loss and brain damages.METHODS:Different doses of bilirubin solution(30 mg/kg,60 mg/kg,90 mg/kg,120 mg/kg and 150 mg/kg) were injected into the abdominal cavity of 15-day old SD rats to make the animal model of hyperbilirubinemia.The serum concentrations of bilirubin were detected by a micro-gauge.The bilirubin concentrations in the brain tissues were examined via a diazo method.The Na+-K+ATPase activities in the brain tissues were analyzed by rooting phosphorus.The NO contents in the brain tissues were assayed via the method of nitrate reductase.BAEP were recorded with an evoked potential recorder.RESULTS:After making the ejection,parts of the rats in the high dosage groups(120 mg/kg and 150 mg/kg) showed the abnormal neuro-behaviors.After 6 hours of the ejection,the bilirubin concentrations in serum and in brain tissues,and NO contents in the brain tissues were increased significantly.The Na+-K+ATPase activities in the brain tissues were decreased obviously,and the PL and IPL of BAEP were prolonged significantly in all the experimental rats except the ones in low dosage group(30 mg/kg).The changes of them were closely related to the dose of injected bilirubin.CONCLUSION:The PL and IPL of BAEP are the objective and sensitive indexes for early monitoring the hearing loss and brain damages in hyperbilirubinemia.NO may plays a certain role in the pathogenesis of bilirubin induced hearing loss and brain damages.

Objective To identify the miR-122 which regulateing GATA4 expression during the induction of rat bone marrow mesenchymal stem cells (bMSCs) differentiating into cardiomyocyte-like cells. Methods BMSCs were isolat-ed from bone marrow and induced to differentiate into cardiomyocyte-like cells using 5-azacytidine. The miR-122 which may regulate expression of GATA4 were predicted using miRanda and TargetScan softwares and identified by dual luciferase report system. The expressions of miR-122 and GATA4 were determined using q-PCR during the differentiation of bMSCs into cardiomyocyte-like cells. Results The induced cells were completely in contacted with adjoining cells and uniform in shape and aligned parallelly. Cardiac troponin I (cTnI) expression was detected by immunofluorescence cytochemistry. Using dual luciferase reporter system in vitro, miR-122 were proved to be able to effectively inhibit GATA4 expression by binding the 3′UTR of GATA4 mRNA. q-PCR results showed that the expression of miR-122 is negatively correlated with that of GATA4 mRNA transcription. Conclusion These results indicated that miR-122 regulate the expression of GATA4 during the induction of cardiomyocyte-like cells.

AIM: To observe the relationship between noradrenaline and the synaptic configuration in rat hippocampus CA3 area. METHODS: Noradrenergic system injured models were produced by injecting 6-hydroxydopamine into rats' bilateral dorsal noradrenergic bundle. Then Y-type maze tests and elicitation of P3-like were carried out respectively before and after the model was established. The parameters of synaptic configuration in the hippocampus CA3 areas were also analyzed quantitatively. RESULTS: The decreases in the thickness of postsynaptic density material, the curvature of synaptic interface and the occurrence of perforated synapses, and the increase in the width of synaptic cleft were observed. CONCLUSION: The normal noradrenalin level in hippocampus is necessary to maintain the normal synaptic interface ultrastructure in hippocampus CA3 area.

ObjectiveTo systematically evaluate the clinical effect of epidermal growth factor receptor (EGFR)-targeted agents in the treatment of advanced pancreatic cancer. MethodsEMbase, PubMed, Cochrane Library, Clinical Trials, CNKI, Wanfang Data, and VIP were searched for randomized controlled trials (RCTs) of EGFR-targeted therapies for advanced pancreatic cancer. Eligible RCTs were screened out based on quality and related criteria, and RevMan 5.3 and STATA 12.0 were used to perform the meta-analysis. ResultsA total of 8 RCTs were included, with 2382 patients in total. The results of the meta-analysis showed that compared with the control group, the experimental group had no increases in overall survival time (hazard ratio ［HR］=0.86, 95% confidence interval ［CI］: 0.74-1.02, P＞0.05) and objective response rate (risk ratio ［RR］=1.00, 95%CI: 0.76-1.32, P＞0.05), but had significant increases in progression-free survival time (HR=0.78, 95%CI: 0.62-0.98, P＜0.05) and disease control rate (RR=1.22, 95%CI: 1.04-1.43, P＜0.05). The subgroup analysis showed that after the source of heterogeneity was identified and the studies with high heterogeneity were excluded, the experimental group had a significant increase in overall survival time (HR=0.85, 95%CI: 0.77-0.94, P＜0.05), and the patients with rash appeared to be more sensitive to the therapies (HR=0.70, 95%CI: 0.54-0.92, P＜0.05). ConclusionFor patients with advanced pancreatic cancer, EGFR-targeted therapies can effectively prolong overall survival time and improve quality of life.

On March 24, 2017, a patient with Von Hippel-Lindau syndrome (VHL) characterized by bilateral adrenal pheochromocytoma and pancreatic tumors was admitted to our hospital, who underwent simultaneous pancreatic body and tail tumor resection, bilateral adrenal tumor resection and Omentum transplantation of the right adrenal gland.Intraoperative hormone therapy was used. Part of the normal adrenal tissue was preserved and embedded in the omentum, but an adrenal crisis occurred on the first day after the operation.The hormone replacement was used. Postoperative hormone replacement therapy was performed for 6 months. After 4 years of follow-up, blood pressure was normal, no cortical dysfunction, no tumor recurrence or other related lesions appeared. The preserved part of adrenal tissue during simultaneous multi-organ tumor resection for such patients can reduce long-term hormone replacement after surgery and prevent late adrenal cortex dysfunction.

Objective: To observe the effects of oxymatrine(OM) on the expression and release of high mobility group box 1(HMGB1) in rat pancreatic acinar cell line AR42J stimulated by hydrogen peroxide. Methods: MTT method was used to detect the effects of H₂O₂ in different concentrations on the survival of AR42J cells. AR42J cells cultured in vitro were divided into control group, H₂O₂ group and H₂O₂+ OM group. An equal volume of H₂O₂(final concentration 0.16 mmol/L) was added in H₂O₂ group and H₂O₂+ OM group, respectively, while an equal volume of triple distilled water was added in control group. In H₂O₂+ OM group, OM(final concentration 0.5 g/L)was added 0.5 h before the addition of H₂O₂, and cell samples and supernatant were collected after 24 h culture. The expression of HMGB1 protein was detected by Western blotting, the level of HMGB1 protein in cell supernatant was detected by enzyme-linked immunosorbent assay, and the intracellular distribution of HMGB1 protein was detected by immunofluorescence. Results: In the H₂O₂ group, the expression of HMGB1, the secretion of HMGB1 in the supernatant and the proportion of cytoplasmic HMGB1 in the total HMGB1 were significantly higher than those in the control group[1.04±0.04 vs 0.69±0.02, (4.84±0.13)μg/L vs (2.68±0.07)μg/L, (35.7±2.5)% vs (10.7±1.9)%], and all the differences were statistically significant (all P<0.05). After OM intervention, HMGB1 protein expression, secretion and cytoplasmic proportion were [0.82±0.02, (3.97±0.10)μg/L and (27.3±1.7)%], respectively, which were obviously lower than those in the H₂O₂ group, and all the differences were statistically significant (all P<0.05). Conclusions H₂O₂ can induce the expression and release of HMGB1 in rat pancreatic acinar cells; OM treatment could alleviate the severity of oxidative stress injuries induced by H₂O₂ in AR42J cells.

The rapid and accurate authentication of traditional Chinese medicines(TCMs)has always been a key scientific and technical problem in the field of pharmaceutical analysis.Herein,a novel heating online extraction electrospray ionization mass spectrometry(H-oEESI-MS)was developed for the rapid and direct analysis of extremely complex substances without the requirement for any sample pretreatment or pre-separation steps.The overall molecular profile and fragment structure features of various herbal medicines could be completely captured within 10-15 s,with minimal sample(＜0.5 mg)and solvent consumption(＜20 μL for one sample).Furthermore,a rapid differentiation and authentication strategy for TCMs based on H-oEESI-MS was proposed,including metabolic profile characterization,characteristic marker screening and identification,and multivariate statistical analysis model validation.In an analysis of 52 batches of seven types of Aconitum medicinal materials,20 and 21 key compounds were screened out as the characteristic markers of raw and processed Aconitum herbal medicines,respectively,and the possible structures of all the characteristic markers were comprehensively identified based on Com-pound Discoverer databases.Finally,multivariate statistical analysis showed that all the different types of herbal medicines were well differentiated and identified(R2X＞0.87,R2Y＞0.91,and Q2＞0.72),which further verified the feasibility and reliability of this comprehensive strategy for the rapid authentication of different TCMs based on H-oEESI-MS.In summary,this rapid authentication strategy realized the ultra-high-throughput,low-cost,and standardized detection of various complex TCMs for the first time,thereby demonstrating wide applicability and value for the development of quality standards for TCMs.

ObjectiveTo compare wild and cultivated Paeoniae Radix Rubra（PRR） in three aspects， including character， microscope， determination of primary and secondary metabolites. MethodSeventeen batches of wild and nine batches of cultivated PRR were collected，their character data were measured by vernier caliper and scales， and their paraffin sections were made by safranin-fixed green dyeing for the observation of microscopic features. The content of ethanol-soluble extracts and total tannin from wild and cultivated PRR was determined by the method of general principle 2201 and 2202 in the 2020 edition of Chinese Pharmacopoeia， the content of polysaccharides was determined by phenol-sulfuric acid method. Anthrone colorimetry was used to determine the content of starch， and Van Soest method of washing fiber was used to determine the content of fiber. The contents of fructose， glucose and sucrose in wild and cultivated PRR were determined by ultra-high performance liquid chromatography evaporative light scattering detection（UPLC-ELSD）， and the secondary metabolites（gallic acid， methyl gallate， catechin， oxypaeoniflorin， albiflorin， paeoniflorin， ellagic acid， 1，3，4，6-tetragalloylglucose， galloylpaeoniflorin， 1，2，3，4，6-O-pentagalloylglucose， naringenin， benzoylpaeoniflorin and benzoylalbiflorin） were determined by UPLC. Principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to analyze the data of wild and cultivated PRR， the contribution of different factors to the difference was determined according to the variable importance in the projection（VIP） value>1 and P<0.05. ResultIn term of characters， wild PRR showed the traditional characteristic of Zaopi Fencha， its outer skin was loose and easy to fall off， its surface had longitudinal furrow and wrinkle， but the outer skin of cultivated PRR was not easy to fall off， and its surface was relatively smooth. The radial texture of xylem of wild PRR cross-section was more obvious， showing radial striations， vacuoles and more cracks， while the radial texture of xylem of cultivated PRR cross-section was not obvious， dense and some had cracks. Microscopically， the number of radial vessels arranged in the xylem of wild PRR was more than that of cultivated PRR， the number of calcium oxalate clusters in the phloem and xylem of wild PRR was more than that of cultivated PRR， while the number of starch grains was significantly higher in cultivated PRR. In terms of the content of primary chemical constituents， the contents of polysaccharides and starch of cultivated PRR were significantly higher than those of wild PRR（P<0.05）， while the contents of cellulose， lignin， fructose and glucose of wild PRR were significantly higher than those of cultivated PRR（P<0.05）. The results of determination of 13 secondary metabolites showed that the contents of paeoniflorin， methyl gallate， catechin and oxypaeoniflorin in wild PRR were significantly higher than those in cultivated PRR（P<0.05）， while the contents of albiflorin， gallic acid， ellagic acid， naringenin， benzoylpaeoniflorin and benzoylalbiflorin were significantly lower than those of cultivated PRR（P<0.05）. A total of 10 variables contributing to the differentiation between wild and cultivated PRR were screened， including albiflorin， cellulose， benzoylpaeoniflorin， oxypaeoniflorin， naringenin， ellagic acid， starch， lignin， paeoniflorin and total tannins. ConclusionThere are significant differences between wild and cultivated PRR in characters， microscopic characteristics， contents of primary and secondary metabolites. It is suggested that the content ratio of paeoniflorin and albiflorin， the contents of oxypaeoniflorin and cellulose can be used as indicators to characterize production methods of PRR so as to improve the quality standard of PRR. This study can provide reference for the improvement of quality standard of PRR and the guidance of high quality production of PRR.