ObjectiveTo evaluate the clinical efficacy and safety of Xiaozhen Formula （消疹方） in preventing skin toxicity induced by epidermal growth factor receptor inhibitors （EGFRIs） in patients with EGFR-mutant non-small cell lung cancer （NSCLC）. MethodsA randomized， double-blind， placebo-controlled， multicenter clinical study was conducted. A total of 120 patients with EGFR-mutant NSCLC from seven centers were enrolled and randomly assigned to a treatment group （60 cases） or a control group （60 cases）. On the basis of EGFRI-targeted therapy， patients in the treatment group received Xiaozhen Formula granules， whereas those in the control group received Xiaozhen Formula placebo granules， both at 10 g twice daily for 4 consecutive weeks. The primary outcomes were the grading of skin toxicity evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events （NCI-CTCAE） version 5.0 and the incidence of rash. Secondary outcomes included the time to onset and time to resolution of the highest-grade rash， the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 （EORTC QLQ-C30） scores， the Hospital Anxiety and Depression Scale （HADS） scores， and disease control rate， together with safety assessments. ResultsBased on the full analysis set （FAS）， the incidence of skin toxicity in the treatment group was 18.33% （11/60）， significantly lower than 45.00% （27/60） in the control group （P＜0.01）， with the highest severity of skin toxicity in both groups was grade 2. Among patients who developed rash， the resolution rate in the treatment group was 90.91% （10/11）， higher than that 33.33% （9/27） in the control group. The median time to resolution was 15 days （95%CI： 8-17 days） in the treatment group and it was not reached in the control group； the distribution of time to resolution differed significantly between groups （P＜0.001）. After treatment， the treatment group had higher EORTC QLQ-C30 functional scale and global health status/quality-of-life scores， and lower symptom scale， single-item scores， as well as HADS-A， and HADS-D scores than the control group （P＜0.05）. In the FAS analysis， the disease control rate （DCR） was 85.0% （51/60） in the treatment group， lower than 100.0% （60/60） in the control group （P=0.003）， whereas no significant between-group difference was observed in the per-protocol set （PPS） analysis （P=0.464）. The incidence of adverse events did not differ significantly between the two groups （P＞0.05）， and no definite safety signals related to the investigational drug were observed. ConclusionXiaozhen Formula can reduce the incidence of EGFRI-induced skin toxicity， and improve the outcome of rash regression， the patients' quality of life and psychological status in EGFR-mutant NSCLC patients.

Objective To duplicate the existing model of intracranial oculomotor nerve injury in rats,and propose a new method of orbital cavity clamping oculomotor nerve,evaluate the respective advantages of the two models.Methods Male SD rats were used as experimental animals,and two different methods of preparing oculomotor nerve injury models were compared.Sphenopalatine foramen approach group:clamp the initial segment of the oculomotor nerve from the opening of the upper edge of the orbit for 10 s.The skull base approach group,the temporal bone was removed and the infratentorial segment of the oculomotor nerve was clampped for 10 s.Taking the success rate,survival rate and survival status of the model rats as observation indicators,the applicability of the model rats to the intervention of gastric perfusion was and intraorbital electroacupuncture evaluated.Results The success rate after molding 24 h:In the sphenopalatine foramen approach group was 92.31%(12/13);In the skull base approach group was 34.29%(12/35).Survival rate:7 d after gavage:In the sphenopalatine foramen approach group,6 patients survived,with a survival rate of 100.00%(6/6).Four patients survived in the skull base approach group,with a survival rate of 66.67%(4/6).7 days after orbital electroacupuncture:Five patients survived in the sphenopalatine foramen approach group(83.33%,5/6).Three patients survived in the skull base approach group,with a survival rate of 50.00%(3/6).Survival state of rats(0-20 points,the smaller the score,the better):24 h after modeling,the status score of sphenopalatine foramina approach group was 4.11±0.90,and that of skull base approach group was 12.39±1.378.After 7 days of intragastric administration,the score of sphenopalatine foramina approach group was 2.50±1.05,and the score of skull base approach group was 14.50±0.58.The score of sphenopalatine foramina approach group was 2.00±1.22 and the score of skull base approach group was 15.33±0.58 after 7 days of intraorbital electroacupuncture intervention.The success rate,survival rate and survival state of rats in sphenopalatine foramina approach group were better than those in skull base approach group 24 h after modeling(P<0.05);The survival rate and survival state of rats in sphenopalatine foramina approach group were better than those in skull base approach group 7 days after gavage and orbital electroacupuncture intervention(P<0.05).Conclusion The model of oculomotor nerve injury prepared by sphenopalatine foramina approach is more suitable for the basic research of nerve repair after the intervention of gastric gavage and orbital electroacupuncture.The model rats with oculomotor nerve injury prepared by the base approach are more suitable for the basic research after the injury of the intracranial segment of the oculomotor nerve.

Objective:To investigate the feasibility of 3.0 T glutamate chemical exchange saturation transfer (GluCEST) imaging in evaluating renal redox metabolism in renal ischemia-reperfusion injury (IRI).Methods:Rabbits in the IRI group ( n=56) underwent surgery by clamping the left renal artery for 45 min and then releasing to establish IRI. Rabbits in the sham group ( n=8) underwent the same operation without clamping the left renal artery. GluCEST MRI was performed before and at 1 h, 12 h, 1 day, 3 days, 7 days, and 14 days after the operations, with eight rabbits in the IRI group sacrificed immediately after each scanning and eight in the sham group sacrificed at 14 days after scanning. The left kidneys were removed for histopathological examination and reactive oxygen species (ROS) fluorescence staining. Differences in the magnetic resonance ratio asymmetry (MTR asym) of the renal cortex and outer medulla among different groups were compared. Correlations between the MTR asym and ROS were analyzed. Results:The MTR asym of the renal cortex in the sham and IRI subgroups were higher than that of the outer medulla ( t=8.16, P<0.001; t=4.78, P=0.002; t=4.94, P=0.002; t=5.76, P=0.001, t=6.68, P<0.001; t=6.40, P<0.001; t=5.16, P=0.001; t=3.30, P=0.013). The MTR asym of the renal cortex and outer medulla in the IRI-1h, IRI-12h, IRI-1d, IRI-3d, IRI-7d, and IRI-14d groups were lower than in the sham and IRI-pre groups (all P<0.05). The MTR asym of the renal cortex and outer medulla in the IRI-1h group were lower than in the IRI-12h, IRI-1d, IRI-3d, IRI-7d, and IRI-14d groups (all P<0.05). The MTR asym of the renal cortex in the IRI-12h group was lower than in the IRI-7d and IRI-14d groups (1.84%±0.09% vs.2.42%±0.19%, 2.41%±0.31%, all P<0.05). The MTR asym of the renal cortex in the IRI-1d group was lower than in the IRI-7d group (1.99%±0.17% vs. 2.42%±0.19%, P=0.008). The MTR asym of the outer medulla in the IRI-12h group was lower than in the IRI-3d, IRI-7d, and IRI-14d groups (1.32%±0.27% vs. 1.79%±0.31%, 1.98%±0.18%, 1.66%±0.40%, respectively, all P<0.05]. The MTR asym of the outer medulla in the IRI-7d group was higher than in the IRI-1d and IRI-14d groups (1.98%±0.18% vs. 1.52%±0.31%, 1.66%±0.40%, all P<0.05). The MTR asym of the renal cortex and outer medulla had a strong negative correlation with the mean fluorescence intensity of ROS ( ρ=-0.889, P<0.001; ρ=-0.784, P<0.001). Conclusion:3.0 T GluCEST imaging can indirectly reflect the changes of renal redox metabolism in renal IRI.

Objective:To explore the feasibility of chemical exchange saturation transfer (CEST) imaging at 3.0 T MRI in quantifying renal redox metabolism in vitro models and experimental animals.Methods:Redox metabolites in vitro models with physiological concentrations were prepared, including reduced metabolites (glutamate, alanine, glutathione) and oxidized metabolites (2-ketoglutarate, pyruvate, glutathione disulfide, ammonium hydroxide). CEST examinations were performed at 3.0 T MRI. The imaging parameters were as follows: CEST images with different saturation pulse intensity (B 1) (1, 2, 3, 4 μT) and a fixed radio frequency (RF) duration of 2 000 ms; CEST images with different RF durations (1 500 and 2 000 ms) were acquired with a fixed B 1 value of 2 μT to obtain the optimal scanning parameters. CEST examinations with optimized parameters were performed on the left kidneys of seven healthy rabbits, and the differences in magnetic resonance ratio asymmetry (MTR asym) between rabbit renal cortex and outer medulla were measured. A paired t-test was used to compare the differences. Results:The optimal B 1 for CEST examination of redox metabolites was 2 μT, and the optimal RF duration was 2 000 ms. The MTR asym peaks of glutathione disulfide, glutathione, glutamic acid, and alanine were at 3.75, 3.5, 3, and 1.5 ppm, respectively. The MTR asym peaks of pyruvate, 2-ketoglutarate, and ammonium hydroxide were at 1 ppm. The MTR asym peak values of reduced metabolites were higher than those of oxidized metabolites. When the B 1 value was 2 μT and the RF duration was 2 000 ms, the MTR asym signal of the renal cortex was (2.60±1.10) %, (2.86±1.32) %, (3.04±1.06) %, and (2.98±0.91) % at 1, 3, 3.5, and 3.75 ppm, respectively. The MTR asym signal of the outer medulla was (1.00±0.56) %, (2.43±0.94) %, (2.29±0.88) % and (1.98±0.58) %, respectively. The MTR asym signal of the renal cortex was higher than that of the outer medulla, and the differences were statistically significant ( t=3.04, P=0.023; t=2.56, P=0.043; t=3.50, P=0.013; t=3.45, P=0.014). Conclusion:CEST imaging at 3.0 T MRI can be used to quantitatively evaluate redox metabolism of healthy rabbit kidneys in vitro model and normal experimental rabbits.

Objective:To study and analyse the results of postoperative hemorrhage after laparoscopic pancreaticoduodenectomy (LPD).Methods:The clinical data of patients who underwent LPD from May 2011 to December 2019 at Hunan Provincial People's Hospital were retrospectively analyzed. The clinical characteristics of patients, onset time of postoperative hemorrhage, location of postoperative hemorrhage, postoperative biliary fistula, pancreatic fistula, infection and other short-term complications, reoperation and mortality rates were analyzed.Results:Of 356 patients who underwent LPD in this study, there were 200 males and 156 females, aged (58.0±10.5) years. The postoperative complication rate was 33.1% (118/356), the reoperation rate was 6.5% (23/356), and the mortality rate was 2.5% (9/356). The most common complications were postoperative hemorrhage [15.2% (54/356)], pancreatic fistula [14.6%(52/356)] and abdominal infection [13.8%(49/356)]. The onset time of postoperative hemorrhage was usually in the 1st - 14th day, and the highest rate of postoperative hemorrhage was 3.9% (14/356) on the first day after surgery. The postoperative hemorrhage rate then showed a downward trend, but increased again on the 7th day. The extraluminal hemorrhage locations were relatively widely distributed, and the incidence of gastrointestinal anastomotic hemorrhage in patients with intraluminal hemorrhage was the highest [67.9%(19/28)]. Of the 9 patients who died, 7 were related to postoperative bleeding.Conclusions:LPD resulted in a high incidence of complications. Postoperative hemorrhage was a complication that had the greatest impact on short-term recovery of patients. It was also an important cause of reoperation and death. In addition to postoperative bleeding caused by pancreatic fistula, gastrointestinal anastomotic bleeding was also clinically important.

The technique of "simulative habitat cultivation" is to preserve the quality of traditional Chinese medicine by simulating the original habitat and site environment of wild Chinese medicine resources. Dendrobium nobile is the most representative variety of traditional Chinese medicine which reflects the coordinated development of medicinal material production and ecological environment. In this paper, the main technical points of the simulated cultivation model of D. nobile were summarized as follows: rapid propagation of seedling tissue technology to ensure the genetic stability of provenance; line card+fermented cow manure+live moss method to improve the survival rate; epiphytic stone cultivation to improve the quality of medicinal materials; and the integration of mycorrhizal fungi to improve the quality stability of medicinal materials. On the basis of summarizing the ecological benefits, economical and social benefits generated by the application of the technology, the paper systematically analyzes the principle of the technology for the cultivation of D. nobile to promote the excellent quality, the light, gas, heat and fertilizer resources of the undergrowth niche are in line with the wild site environment of D. nobile. The rich and complex soil microbial community in the forest laid the foundation for the species diversity needed for the growth of D. nobile.The stress effect on the growth of D. nobile resulted in the accumulation of secondary metabolites. The symbiotic relationship between the symbiotic fungi such as bryophytes and D. nobile promotes the synthesis of plant secondary metabolites. The high quality D. nobile was produced efficiently by improving and optimizing the cultivation techniques.
Animals ; Cattle ; Dendrobium ; Ecosystem ; Female ; Medicine, Chinese Traditional ; Mycorrhizae ; Symbiosis

Objective: To evaluate the similarity of Cocculus orbiculatus root and stem by high performance liquid chromatography (HPLC) fingerprint, and to provide a reference for evaluation and clinical application of C. orbiculatus root and stem. Methods: HPLC was applied to chromatographic separation of C. orbiculatus root and stem in different seasons from 14 areas of Guizhou province. The chromatography conditions were: Agilent ODS C18 (250 mm × 4.6 mm, 5 μm) column, mobile phase of CAN 0.1% H3PO4, running time of 95 min, flow speed of 1.0 mL/min, detection wavelength of 254 nm, and column temperature of 30 ℃. The data were processed by Chinese medicine chromatographic fingerprint similarity evaluation system 2.0. Different C. orbiculatus root and stem were subjected to similarity analysis. Results: The chromatography fingerprint of C. orbiculatus root and stem was established and eight common characteristic peaks were demonstrated. The similarities of the chromatography fingerprint were between 0.985-0.998. Conclusion: The chemical compositions of C. orbiculatus root and stem is similar, but the active substances quantity of C. orbiculatus from different regions and seasons are different.

Objective: To promote the comprehensive utilization in the root barks and stem barks of Toddalia asiatica and to establish an HPLC method for the determination of the fingerprints for the root barks and stem barks of T. asiatica. Meanwhile, the similarity was compared by similarity evaluation software based on the fingerprints. Methods: HPLC analysis was performed on C18 (250 mm × 4.6 mm, 5 μm) with acetonitrile and 0.1% aqueous solution of phosphoric acid as mobile phase in gradient mode at the wavelength of 269 nm, and the flow rate was 1 mL/min. The similarity was calculated by comparison on the fingerprints derived from 10 bathes of T. asiatica root barks and 10 bathes of T. asiatica stem barks, all the samples were collected from the different areas in different seasons. Results: The mutualmode of HPLC fingerprints was set up and the similar degrees to the crude drugs of different sources were compared. The content ratio of active ingredients is different from samples in different areas and seasons. Conclusion: The fingerprint similarity is greater than 0.9 between T. asiatica root barks and T. asiatica stem barks, so the compositions are highly similar.

Objective To find the key miRNA that relative to peritoneal fibrosis associated with peritoneal dialysis (PD) by microarray technology,and verify its expression in vitro and in vivo.Methods The peritoneal fibrosis mouse model associated with PD were established by intraperitoneal injection of lipopolysaccharide (LPS)+ 4.25％ peritoneal dialysate.The expression of miRNA was detected by microarray in peritoneal tissues.The expression of miRNA profiles between fibrotic and normal peritoneal tissues was compared.The differentially expressed miRNA (miR-200a) was validated by real-time PCR in lager sample size cohorts.The expressions of miR-200a were also detected in the epithelial-mesenchymal transition (EMT) process of human peritoneal mesothelium cells.Results In mice model of PD,peritoneal tissue was markedly thickened and with a massive extracellular matrix accumulation.In contrast with control,the expression level of epithelial marker E-cadherin was significantly decreased,α-SMA,Col-Ⅰ and FN were remarkably increased (P ＜ 0.05).By miRNA microarray analysis,miR-200a was significantly down-regulated (3.31 folds change,P ＜ 0.05) in fibrotic peritoneal tissues.The down-regulated expression level of miR-200a was also validated by realtime PCR in larger cohorts (P ＜ 0.05).Then,the expression level of miR-200a was detected in the EMT process of human peritoneal mesothelium cells.During the process of TGF-β1 induced EMT,miR -200a was significantly down-regulated compared with the control (P ＜ 0.05).Conclusions Downregulated expression of miR-200a was observed both during peritoneal fibrosis and TGF-β 1 induced EMT in vivo and in vitro,suggesting that miR-200a may be involved in the peritoneum fibrosis by regulating the target genes of EMT.

Objective: To explore the clinical characteristics of ST elevation and non-ST elevation acute myocardial infarction (AMI) related with left circumflex artery (LCX) occlusion. Methods: Clinical data of 86 consecutively enrolled patients with LCX occlusion -related AMI undergoing percutaneous coronary intervention (PCI) were retrospectively analyzed. According to manifestations of electrocardiography, the patients were divided into ST elevation myocardial infarction (STEMI) group (n=32) and non STEMI (NSTEMI) group (n=54). Clinical features and prognosis were compared between two groups. Results: Compared with NSTEMI group, there were significant increase in serum level of creatinine [(80±23) μmmol/L vs. (100±30) μmmol/L], in rates of intra-aortic balloon counterpulsation （IABP）support (3.7% vs. 18.8%), usage of invasive respiratory machine (1.9% vs. 15.6%), ischemic mitral reflux (13.0% vs. 40.6%), complete atrioventricular block (0 vs. 9.4%), proportion of left coronary artery dominant type (7.4% vs. 28.1%) and left ventricular end-diastolic diameter [LVEDd,（46±4）mm vs.（48±5）mm?]; And significant decrease in percentage of triple-vessel coronary disease (72.2% vs. 46.9%) in STEMI group, P<0.05 or <0.01. There was no significant difference in mortality rate during admission (3.1% vs. 0, P>0.05) between STEMI group and NSTEMI group. Conclusions: Compared with patients with NSTEMI, patients with STEMI have poorer heart function in patients with left circumflex artery occlusion, which may be related to more left coronary dominance.