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.

As arsenic widely exists in nature and has been used in the pharmaceutical preparations, the traditional Chinese medicine(TCM) with arsenic include realgar(As_2S_2 or As_4S_4), orpiment(As_2S_3), and white arsenic(As_2O_3). Among the above representative medicine, the TCM compound formulas with realgar are utilized extensively. Just in Chinese Pharmacopoeia(2020 edition), there are 37 Chinese patent medicines including realgar. The traditional element analysis focuses on the detection of the total amount of elements, which neglects the study on the speciation and valence of elements. The activity, toxicity, bioavailability, and metabolic pathways of arsenic in vivo are closely related to the existence of its form, and different forms of arsenic have different effects on organisms. Therefore, the study on the speciation and valence of arsenic is of great importance for arsenic-containing TCMs and their compound formulas. This paper reviewed four aspects of the speciation and valence of arsenic, including property, absorption and metabolism, toxicity, and analytical assay.
Arsenic/analysis* ; Arsenicals/analysis* ; Sulfides ; Arsenic Trioxide ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/analysis* ; Biological Products

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*

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.

BACKGROUND: Extreme temperature events, including extreme cold, are becoming more frequent worldwide, which might be harmful to pregnant women and cause adverse birth outcomes. We aimed to investigate the association between exposure to low ambient temperature in pregnant women and adverse birth outcomes, such as preterm birth, low birth weight, and stillbirth, and to summarize the evidence herein. METHODS: Relevant studies were searched in PubMed, Cochrane, and Embase electronic databases until November 2021. Studies involving low ambient temperature, preterm birth, birth weight, and stillbirth were included. The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses were followed to conduct this study risk of bias and methods for data synthesis. RESULTS: A total of 34 studies were included. First, pregnant women exposed to low ambient temperature had an increased risk of preterm birth (risk ratio [RR] 1.08; 95% confidence interval [CI] 1.04-1.13). Subgroup analyses revealed that exposure during late pregnancy was more likely to induce preterm birth. In addition, only pregnant women exposed to <1st percentile of the mean temperature suffered increased risk of preterm birth. Moreover, pregnant women living in medium or hot areas were more prone to have preterm births than those in cold areas when exposed to low ambient temperatures. Asians and Blacks were more susceptible to low ambient temperatures than Caucasians. Second, pregnant women exposed to low ambient temperature had an increased risk of low birth weight (RR 1.07; 95% CI 1.03-1.12). Third, pregnant women had an increased risk of stillbirth while exposed to low ambient temperature during the entire pregnancy (RR 4.63; 95% CI 3.99-5.38). CONCLUSIONS: Exposure to low ambient temperature during pregnancy increases the risk of adverse birth outcomes. Pregnant women should avoid exposure to extremely low ambient temperature (<1st percentile of the mean temperature), especially in their late pregnancy. This study could provide clues for preventing adverse outcomes from meteorological factors. REGISTRATION No. CRD42021259776 at PROSPERO ( https://www.crd.york.ac.uk/PROSPERO/ ).
Pregnancy ; Infant, Newborn ; Female ; Humans ; Pregnancy Outcome ; Premature Birth/epidemiology* ; Stillbirth/epidemiology* ; Temperature ; Pregnancy Complications

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.