Objective To construct a perioperative exercise program for older frail patients with colorectal cancer,and to verify its effect.Methods Based on Goal-directed Theory and literature review,expert consultation was carried out to establish the perioperative exercise program for older frail patients with colorectal cancer.Then,from July to December 2022,the perioperative exercise program was established for older frail patients with colorectal cancer hospitalized in the General Surgery Department of a tertiary A hospital in Suzhou by convenience sampling method for preliminary application.It was divided in to the intervention group and the control group by the ward.The intervention group was applied with the constructed perioperative exercise program on the basis of routine perioperative nursing.The safety,feasibility and intervention effect of the program were evaluated.Results 15 experts were included for 2 rounds of expert consultations.The authority coefficient was 0.880;the coefficient of variation was＜0.250;the Kendall concordance coefficient was 0.167 and 0.224,respectively.The final program contained 4 stages:preoperative exercise,postoperative bed rest,sitting and standing exercise.In the end,54 specific interventions were constructed.During the preliminary application,all the patients completed the program.Generalized estimation equation showed that,on the interaction effect,there was no statistical difference(P=0.752);there were significant differences on the intervention effect and the time effect(P＜0.05).At discharge,there were significant differences in timed up and go test and Barthel Index between the 2 groups(P＜0.05).Only 2 patients experienced mild pain in the intervention group,and no other adverse events occurred.Conclusion The perioperative exercise program for older frail patients with colorectal cancer,based on Goal-directed Theory,is scientific,reliable and safe.It has been preliminarily verified in improving postoperative physical function,activities of daily living and early postoperative recovery of elderly frail patients with colorectal cancer.

Objective To gain an in-depth understanding of the motivations,patterns,and related factors in family decision-making regarding the referral of terminal patients in tertiary hospitals.Methods Using purposive sampling,terminal patients and their family members from three tertiary hospitals in Beijing were se-lected as subjects.Semi-structured interviews were conducted,and the interview data were subjected to thematic analysis.Results Following the saturation principle,a total of 11 patients and 15 family members were includ-ed.The interview data were organized and analyzed,yielding six major themes:decision premises,decision pat-terns,family support,support from the referring hospital's medical team,referral channel conditions,and in-volvement of volunteer teams and social support.Based on these findings,a flowchart illustrating the family deci-sion-making process for the referral of terminal patients was constructed.Conclusions The study provides a com-prehensive analysis of various factors influencing family decision-making in the referral of terminal patients in ter-tiary hospitals.The results underscore the significance of internal and external factors,emphasizing the integrated impact of decision patterns,family support,medical team support,referral channel conditions,and the in-volvement of volunteer teams and social support.The research offers profound insights into improving the referral process for terminal patients and enhancing the quality of family decision-making.It provides valuable recommen-dations for future improvements in medical services and decision support.

The author analyzed the characteristics of phase Ⅰ clinical trials of macromolecular drugs,the characteristics of evaluation indicators of phase Ⅰ clinical trials of macromolecular drugs,such as safety evaluation,pharmacokinetic and pharmacodynamic evaluation,and efficacy evaluation.And the control points of subjects management,management of experimental macromolecule drugs,and identified and potential risk factors of macromolecule drugs in the implementation of risk management for phase Ⅰ clinical trials of macromolecule drugs were discussed in depth based on previous clinical trial research experience.Through discussion and analysis,the author suggests that each research center can formulate risk control strategies according to the actual situation,improve the efficiency of risk control,and facilitate the smooth implementation of clinical trials and improve the quality of clinical trials.

The Dionex CaboPac^TM PA10 BioLC^TM Analyical 2 mm × 250 mm column was used with a protective column (Dionex CaboPac^TM PA10 BioLC^TM Guard 2 mm × 50 mm). 100 mmol·L^-1 sodium hydroxide solution was used as eluent; the flow rate was 0.25 mL·min^-1. Sample tray temperature: 35 ℃. The pulse amperometric detector was adopted, and the waveform was Gold CWE, Ag-AgCl RE, Carbo, Quad. The samples were cultured with 8 concentrations of glycogen substrates (0.31, 1.25, 2.5, 5, 10, 20, 30, and 40 mg·mL^-1). D-Glucose concentrations were measured at 5 different time points (T0, T1, T2, T3 and T4). The glucose concentration from T1 to T4 minus the glucose concentration at T0. The reaction rate was calculated at different glycogen substrate concentrations. These reaction rates are plotted against substrate concentrations using Michaelis-Menten equation. The kinetic parameters were expressed as V_max (nmol·mg^-1·min^-1) and K_m (mg·mL^-1). The RSD of glucose standard curve R² (n = 6, linear range: 1.25-500 μmol·L^-1) was 0.1% and the RSD (n = 6) of the slope of the standard curve was 2.2%. The mean limit of quantitation was 0.14 μmol·L^-1, and the mean limit of detection was 0.05 μmol·L^-1. The RSD of K_m and V_max were 4.4% and 4.6% respectively in three separate experiments. The durability of the method was good. The method was developed for the on-line automatic determination of the hydrolysis kinetics of acid α-glucosidase (GAA) for injection by ion chromatography. The method has good precision, repeatability and durability, and can be used for the determination of glycogen hydrolysis kinetics of GAA for injection, and could reference value for the enzyme kinetics evaluation of recombinant enzyme replacement therapy.

According to the requirements of the regulatory authorities, degree of modification (DP) should be included in the characterisation of the PEGylated protein drug substance, and is one of the critical quality attributes for quality control. In this study, based on the fundamental assumption that the refractive index (RI) signal and the ultraviolet (UV) signal of PEGylated protein are equal to the sum of the corresponding signal produced by the polyethylene glycol (PEG) and protein parts of the conjugates in their uncoupled state, we developed a method to determine the DP of PEGylated recombinant human growth hormone (inpegsomatropin). In this method, 20 μL of 1 mg·mL^-1 human growth hormone (hGH) standard, 2 mg·mL^-1 PEG reference substance and 1 mg·mL^-1 drug substance solution were each injected to size exclusion chromatographic (SEC) column for separation, detected with ultraviolet and refractive index (UV-RI) detectors in series. Finally, the DP was calculated as the formula derived from the fundamental assumption. The developed SEC-UV-RI method showed good specificity, repeatability (RSD = 0.63%, n = 9) and accuracy, with a recovery of 100.0%, compared with the result obtained from the simultaneously established classical acid hydrolysis method, demonstrating pretty handleability and accessibility, and is appropriate for quality control test of DP for this drug substance.

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
Male ; Humans ; Middle Aged ; Atorvastatin/therapeutic use* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Hypercholesterolemia/drug therapy* ; Cholesterol, LDL/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome ; Triglycerides ; Apolipoproteins B/therapeutic use* ; Double-Blind Method ; Pyrroles/therapeutic use*

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

Objective:To explore the application effect of "connections, concepts, concrete practice and conclusions (4C)" teaching method combined with two-way evaluation method in nursing teaching of gastrointestinal surgery, so as to provide reference for personnel training and quality control of practice.Methods:A historical controlled study was conducted to prospectively include the nursing interns received by the Department of Gastrointestinal Surgery of the hospital from May 2020 to May 2022 as the subjects of this study. The interns were divided into the control group (64 interns from May 2020 to May 2021) and the research group (93 interns from June 2021 to May 2022) according to the order of admission of nursing interns. The control group was taught by traditional nursing teaching method, while the research group was taught by "4C" teaching method combined with two-way evaluation method. The scores of theoretical knowledge and operation of nursing students in the two groups were compared after 6 weeks of practice. The self-directed learning ability of nursing students in the two groups was compared before and after 6 weeks of practice [Chinese version of self-rating scale of self-directed learning (SRSSDL)]. The evaluation of teaching quality between two groups of nursing students were compared. SPSS 25.0 was used for t-test and Chi-square test. Results:One person in the control group voluntarily quit the internship, and two in the observation group voluntarily quit the internship. Finally, 63 people in the control group and 91 people in the research group entered the study. There was no statistical significant difference between the two groups in baseline data ( P>0.05). At 6 weeks of practice, the scores of theoretical knowledge (87.96±4.62) and operation (92.60±4.25) in the study group were higher than those in the control group [(86.02±4.53) and (88.27±4.31)] ( P<0.05). At 6 weeks of practice, the total scores of learning awareness, learning behavior, learning strategies, learning evaluation, interpersonal skills and self-directed learning ability of the two groups were higher than those before practice, and the study group was higher than the control group ( P<0.05). After 2 weeks, 4 weeks and 6 weeks of practice, the scores of the two groups of nursing students in evaluating the teaching quality of the teachers increased gradually compared with that of the first week of practice ( P<0.05). Conclusion:The "4C" teaching method combined with the two-way evaluation method in the nursing teaching of gastrointestinal surgery can improve the nursing students' theoretical knowledge, practical operation ability and self-directed learning ability, and is conducive to the improvement of teaching quality.

Objective:To explore the application of understanding teaching mode combined with hierarchical training in the standardized training of nurses in gastrointestinal surgery department.Methods:Sixty-three nurses who had standardized training in gastrointestinal surgery department in West China Hospital, Sichuan University from January 2018 to January 2022 were selected as the study objects, among which, 32 nurses from January 2018 to July 2020 were set as the control group, taking regular training method, and 31 nurses from August 2020 to January 2022 were set as the observation group, taking the understanding teaching mode combined with hierarchical training method. The core competence scores of the two groups after training were compared, the scores of basic theory and practical skills of the two groups were compared, and the satisfaction degree of nurses during training was compared between the two groups. SPSS 22.0 was used to perform t-test. Results:After the training, the scores of core competence in the observation group were higher than that in the control group, and the difference was statistically significant ( P < 0.05). The scores of theoretical assessment (96.59±3.22) and practical skills (97.09±2.88) in the observation group were significantly higher than those in the control group (91.52±2.45)(91.14±2.85) ( P < 0.05). The total satisfaction scores of the observation group (93.48 ± 2.52) was higher than that of the control group (86.80 ± 2.22), and the difference was statistically significant ( P < 0.05). Conclusion:It is suggested that understanding teaching mode and joint hierarchical training can improve the core ability and assessment score of nurses in gastrointestinal surgery department, and improve the satisfaction of nurses.

A new class of potent liver injury protective compounds, phychetins A-D ( 1- 4) featuring an unique 6/6/5/6/5 pentacyclic framework, were isolated and structurally characterized from a Chinese medicinal plant Phyllanthus franchetianus. Compounds 2- 4 are three pairs of enantiomers that were initially obtained in a racemic manner, and were further separated by chiral HPLC preparation. Compounds 1- 4 were proposed to be originated biosynthetically from a coexisting lignan via an intramolecular Friedel-Crafts reaction as the key step. A bioinspired total synthesis strategy was thus designated, and allowed the effective syntheses of compounds 2- 4 in high yields. Some of compounds exhibited significant anti-inflammatory activities in vitro via suppressing the production of pro-inflammatory cytokine IL-1β. Notably, compound 4, the most active enantiomeric pair in vitro, displayed prominent potent protecting activity against liver injury at a low dose of 3 mg/kg in mice, which could serve as a promising lead for the development of acute liver injury therapeutic agent.