OBJECTIVES: To assess the efficacy and safety of Tiaozhou Ziyin (TZZY) recipe for treatment of premature ovarian insufficiency (POI) and explore the possible mechanisms. METHODS: We used bioinformatics analyses and network pharmacology to identify the main active ingredients in TZZY recipe and their core targets, which were verified by Western blotting. We tested the efficacy and safety of the recipe in 60 POI patients, who were randomized into control group (n=30) with Femoston treatment and TZZY group (n=30) with additional TZZY recipe treatment for 3 menstrual cycles. RESULTS: The core active ingredients of TZZY recipe included kaempferol, β-sitosterol, luteolin, and quercetin. The core targets included SRC, TP53, STAT3, PIK3CA, and MAPK3, which were involved in positive regulation of cell movement and protein phosphorylation, the cancer pathways and the PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had good binding ability with the core targets. In female rat models of POI, TZZY recipe treatment significantly up-regulated ovarian expressions of p-PI3K and p-Akt proteins. In the clinical trial, treatment with Femoston and Femoston plus TZZY recipe both significantly increased E₂ levels and reduced FSH and LH levels and Kupperman scores of the patients, and the combined treatment produced significantly stronger effects. Both treatments increased the number of antral follicles of the patients, but the combined treatment also significantly increased the levels of AMH. CONCLUSIONS The therapeutic mechanism of TZZY recipe for POI involves multiple active ingredients, multiple therapeutic targets and multiple pathways, and activating the PI3K /Akt pathway is one of its main mechanisms of action, to improve ovarian reserve function, alleviate clinical symptoms, and enhance clinical efficacy in POI patients.
Female ; Primary Ovarian Insufficiency/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Rats ; Molecular Docking Simulation ; Signal Transduction ; Sitosterols/therapeutic use* ; Kaempferols/therapeutic use*

Objective:To investigate the effect of ribonucleotide reductase regulatory subunit M2 (RRM2) on the malignant biological behavior and aerobic glycolysis of gastric cancer cells by regulating cyclin-dependent kinase (CDK) 1.Methods:Human gastric cancer MKN-45 cells were divided into si-NC group (transfected with blank fragment) , CoCl 2+si-NC group (hypoxia control transfected with blank fragment) , CoCl 2+si-RRM2 group (hypoxia with RRM2 silencing) , CoCl 2+si-RRM2+pcDNA3.1 NC group (hypoxia with RRM2 silencing and blank vector) and CoCl 2+si-RRM2+pcDNA3.1 CDK1 group (hypoxia with RRM2 silencing and CDK1 overexpression) . The mRNA relative expression levels of RRM2 and CDK1 were analyzed by real time fluorescent quantitative reverse transcription PCR. Co-immunoprecipitation (CoIP) was used to analyze the interaction between RRM2 and CDK1 protein. MTT assay was used to analyze the proliferation activity of cells. The cell migration distance was detected by cell scratch assay. Cell apoptosis was detected by flow cytometry. Adenosine triphosphate (ATP) and glucose kit were used to detect ATP production and glucose consumption. The protein expressions of ENO1, RRM2, HK2, PKM2, GLUT1 and p-CDK1/CDK1 were detected by Western blotting. Results:Real time fluorescent quantitative reverse transcription PCR results showed that the relative expression levels of CDK1 mRNA in si-NC group, CoCl 2+si-NC group and CoCl 2+si-RRM2 group were 1.01±0.15, 1.30±0.06 and 0.51±0.18, and the relative expression levels of RRM2 mRNA were 1.03±0.32, 1.59±0.28 and 0.44±0.17, respectively, and there were statistically significant differences ( F=25.52, P=0.001; F=14.47, P=0.005) . The mRNA expressions of RRM2 and CDK1 in CoCl 2+si-NC group were higher than those in si-NC group. Compared with the si-NC group and the CoCl 2+si-NC group, the mRNA expressions of RRM2 and CDK1 were lower in the CoCl 2+si-RRM2 group (all P<0.05) . CoIP results showed that there was interaction between RRM2 and CDK1. MTT assay, cell scratch assay and flow cytometry showed that the cell proliferation activity of si-NC group, CoCl 2+si-NC group, CoCl 2+si-RRM2 group, CoCl 2+si-RRM2+pcDNA3.1 NC group and CoCl 2+si-RRM2+pcDNA3.1 CDK1 group were 1.04±0.01, 1.18±0.04, 0.84±0.03, 0.81±0.03 and 0.93±0.05, respectively. The cell migration distances were (301.83±2.75) , (369.67±0.76) , (176.50±6.38) , (175.83±3.69) , (254.17±1.61) μm, respectively. The apoptosis rates were 8.05%±0.21%, 5.75%± 0.20%, 28.28%±0.04%, 30.18%±1.51% and 17.79%±0.22%, respectively, all with statistically significant differences ( F=73.82, P<0.001; F=1 600.01, P<0.001; F=787.15, P<0.001) . Compared with the si-NC group and CoCl 2+si-NC group, the proliferation and migration ability of cells in the CoCl 2+si-RRM2 group, CoCl 2+si-RRM2+pcDNA3.1 NC group and CoCl 2+si-RRM2+pcDNA3.1 CDK1 group were weaker, and the apoptosis rates were higher (all P<0.05) . Compared with the CoCl 2+si-RRM2+pcDNA3.1 NC group, the proliferation and migration ability of cells in the CoCl 2+si-RRM2+pcDNA3.1 CDK1 group were stronger, and the apoptosis rate was lower (all P<0.05) . The results of ATP and glucose detection showed that there were statistically significant differences in the amount of ATP production and glucose consumption among the above five groups ( F=12.53, P<0.001; F=19.21, P<0.001) . Compared with the si-NC group, the glucose consumption of cells was lower in the CoCl 2+si-RRM2+pcDNA3.1 CDK1 group ( P<0.05) . Compared with the CoCl 2+si-NC group, the ATP production and glucose consumption of cells in the CoCl 2+si-RRM2+pcDNA3.1 CDK1 group were lower (both P<0.05) . Compared with the CoCl 2+si-RRM2+pcDNA3.1 NC group, the ATP production and glucose consumption of the CoCl 2+si-RRM2+pcDNA3.1 CDK1 group were higher (both P<0.05) . Western blotting showed that there were statistically significant differences in the protein expressions of ENO1, RRM2, HK2, PKM2, GLUT1, and p-CDK1/CDK1 among the above five groups (all P<0.001) . Compared with the si-NC group and the CoCl 2+si-NC group, the protein expressions of ENO1, RRM2, HK2, PKM2, GLUT1 and p-CDK1/CDK1 in the CoCl 2+si-RRM2+pcDNA3.1 CDK1 group were lower (all P<0.05) . Compared with the CoCl 2+si-RRM2+pcDNA3.1 NC group, the protein expressions of ENO1, RRM2, PKM2, GLUT1 and p-CDK1/CDK1 in the CoCl 2+si-RRM2+pcDNA3.1 CDK1 group were higher (all P<0.05) . Conclusions:Silencing RRM2 can inhibit the malignant biological behavior of gastric cancer cells and the occurrence of aerobic glycolysis by regulating CDK1.

Objective To investigate the protective effect of total flavonoids of Salvia divinorum extract against acetaminophen(APAP)-induced acute liver injury(ALI)and its molecular mechanism.Methods The main chemical constituents of total flavonoids of Salvia divinorum were obtained through literature search,and their pharmacological mechanisms were predicted using bioinformatics analysis.In a mouse model of APAP-induced ALI,the protective effects of 100,200 and 400 mg/kg total flavonoids of Salvia miltiorrhiza and 150 mg/kg bifidus were evaluated by observing changes in blood biochemistry and liver histopathology and detecting expressions of the key proteins in the Nrf2/HO-1 signaling pathway.Results Network pharmacology analysis suggested that the main active components in total flavonoids of Salvia divinorum for regulating APAP-induced liver injury included quercetin,lignocerol,caruric acid,and kaempferol,for which GO function enrichment analysis yielded 632 GO entries,including 472 involving biological processes,42 involving cellular composition,and 118 involving molecular function.KEGG enrichment analysis showed that the total flavonoids of Salvia divinorum regulated APAP-induced liver injury mainly through ferroptosis-related signaling pathway.In mice with APAP-induced ALI,treatment with the total flavonoids significantly lowered ALT and AST levels,improved liver histopathology and inflammatory cell infiltration,reduced iron deposition in liver tissues,improved lipid peroxidation-related indexes,promoted the expressions of Nrf2,HO-1,SLC7A11,and GPX-4 proteins,and inhibited the expression of keap1 protein.Conclusion The total flavonoids of Salvia divinorum alleviate APAP-induced ALI in mice possibly by suppressing hepatocyte ferroptosis via activating the Nrf2/SLC7A11/GPX-4 signaling pathway.

Objective To investigate the protective effect of total flavonoids of Salvia divinorum extract against acetaminophen(APAP)-induced acute liver injury(ALI)and its molecular mechanism.Methods The main chemical constituents of total flavonoids of Salvia divinorum were obtained through literature search,and their pharmacological mechanisms were predicted using bioinformatics analysis.In a mouse model of APAP-induced ALI,the protective effects of 100,200 and 400 mg/kg total flavonoids of Salvia miltiorrhiza and 150 mg/kg bifidus were evaluated by observing changes in blood biochemistry and liver histopathology and detecting expressions of the key proteins in the Nrf2/HO-1 signaling pathway.Results Network pharmacology analysis suggested that the main active components in total flavonoids of Salvia divinorum for regulating APAP-induced liver injury included quercetin,lignocerol,caruric acid,and kaempferol,for which GO function enrichment analysis yielded 632 GO entries,including 472 involving biological processes,42 involving cellular composition,and 118 involving molecular function.KEGG enrichment analysis showed that the total flavonoids of Salvia divinorum regulated APAP-induced liver injury mainly through ferroptosis-related signaling pathway.In mice with APAP-induced ALI,treatment with the total flavonoids significantly lowered ALT and AST levels,improved liver histopathology and inflammatory cell infiltration,reduced iron deposition in liver tissues,improved lipid peroxidation-related indexes,promoted the expressions of Nrf2,HO-1,SLC7A11,and GPX-4 proteins,and inhibited the expression of keap1 protein.Conclusion The total flavonoids of Salvia divinorum alleviate APAP-induced ALI in mice possibly by suppressing hepatocyte ferroptosis via activating the Nrf2/SLC7A11/GPX-4 signaling pathway.

Objective To explore the effect of evidence-based thinking oriented micro-course and case-based learning(CBL)on cultivation of clinical thinking ability of nurses who are taking the standardised nursing training in intensive care unit(ICU)so as to provide a new teaching method in the training of nurses.Methods A total of 72 nurses taking standardised nursing training in ICU of our hospital from November 2021 to October 2023 were selected as the research objects.Thirty-six of nurses who took rotation in the ICU from November 2021 to October 2022 were assigned in the control group,and other 36 nurses who took rotation in the ICU from November 2022 to October 2023 were assigned in the trial group.In the control group,CBL teaching method was adopted in the standardised nursing training,while both of evidence-based thinking oriented micro-course and CBL teaching mothed were adopted in the trial group for the standardised nursing training.The two groups were compared in terms of scores of clinical thinking ability,assessment of theory and clinical skills,as well as nurses'satisfaction with the teaching.Results After the training,nurses in the trial group exhibited significant superiority to the control group in total scores of clinical thinking ability and its three dimensions,critical thinking ability,systematic thinking ability and evidence-based thinking ability(P<0.05 for all).Furthermore,nurses in the trial group achieved significantly higher scores in theoretical assessment and assessment of clinical skills in comparison with those in the control group(P<0.05).Moreover,the trial group reported significantly higher satisfaction with both of the teaching method and learning atmosphere than those of the control group(P<0.05 for both).Conclusion Evidence-based thinking oriented micro-course and CBL teaching method can effectively improve the clinical thinking ability,theoretical knowledge and operational skills among the nurses taking standardised nursing training in ICU.

Introduction::Observational studies have revealed an association between waist circumference (WC) and atrial fibrillation (AF). However, it is difficult to infer a causal relationship from observational studies because the observed associations could be confounded by unknown risk factors. Therefore, the causal role of WC in AF is unclear. This study was designed to investigate the causal association between WC and AF using a two-sample Mendelian randomization (MR) analysis.Methods::In our two-sample MR analysis, the genetic variation used as an instrumental variable for MR was acquired from a genome-wide association study (GWAS) of WC (42 single nucleotide polymorphisms with a genetic significance of P <5 × 10 –8). The data of WC (from the Genetic Investigation of ANthropometric Traits consortium, containing 232,101 participants) and the data of AF (from the European Bioinformatics Institute database, containing 55,114 AF cases and 482,295 controls) were used to assess the causal role of WC on AF. Three different approaches (inverse variance weighted [IVW], MR–Egger, and weighted median regression) were used to ensure that our results more reliable. Results::All three MR analyses provided evidence of a positive causal association between high WC and AF. High WC was suggested to increase the risk of AF based on the IVW method (odds ratio [OR] = 1.43, 95% confidence interval [CI], 1.30–1.58, P = 2.51 × 10 -13). The results of MR–Egger and weighted median regression exhibited similar trends (MR–Egger OR = 1.40 [95% CI, 1.08–1.81], P = 1.61 × 10 -2; weighted median OR = 1.39 [95% CI, 1.21–1.61], P = 1.62 × 10 -6). MR–Egger intercepts and funnel plots showed no directional pleiotropic effects between high WC and AF. Conclusions::Our findings suggest that greater WC is associated with an increased risk of AF. Taking measures to reduce WC may help prevent the occurrence of AF.

Objective To systematically evaluate the risk factors for postoperative delirium after surgery for Stanford type A aortic dissection. Methods We searched the CNKI, SinoMed, Wanfang data, VIP, PubMed, Web of Science, EMbase, The Cochrane Library database from inception to September 2022. Case-control studies, and cohort studies on risk factors for postoperative delirium after surgery for Stanford type A aortic dissection were collected to identify studies about the risk factors for postoperative delirium after surgery for Stanford type A aortic dissection. Quality of the included studies was evaluated by the Newcastle-Ottawa scale (NOS). The meta-analysis was performed by RevMan 5.3 software and Stata 15.0 software. Results A total of 21 studies were included involving 3385 patients. The NOS score was 7-8 points. The results of meta-analysis showed that age (MD=2.58, 95%CI 1.44 to 3.72, P＜0.000 01), male (OR=1.33, 95%CI 1.12 to 1.59, P=0.001), drinking history (OR=1.45, 95%CI 1.04 to 2.04, P=0.03), diabetes history (OR=1.44, 95%CI 1.12 to 1.85, P=0.005), preoperative leukocytes (MD=1.17, 95%CI 0.57 to 1.77), P=0.000 1), operation time (MD=21.82, 95%CI 5.84 to 37.80, P=0.007), deep hypothermic circulatory arrest (DHCA) time (MD=3.02, 95%CI 1.04 to 5.01, P=0.003), aortic occlusion time (MD=8.94, 95%CI 2.91 to 14.97, P=0.004), cardiopulmonary bypass time (MD=13.92, 95%CI 5.92 to 21.91, P=0.0006), ICU stay (MD=2.77, 95%CI 1.55 to 3.99, P＜0.000 01), hospital stay (MD=3.46, 95%CI 2.03 to 4.89, P＜0.0001), APACHEⅡ score (MD=2.76, 95%CI 1.59 to 3.93, P＜0.000 01), ventilation support time (MD=6.10, 95%CI 3.48 to 8.72, P＜0.000 01), hypoxemia (OR=2.32, 95%CI 1.40 to 3.82, P=0.001), the minimum postoperative oxygenation index (MD=−79.52, 95%CI −125.80 to −33.24, P=0.000 8), blood oxygen saturation (MD=−3.50, 95%CI −4.49 to −2.51, P＜0.000 01), postoperative hemoglobin (MD=−6.35, 95%CI −9.21 to −3.50, P＜0.000 1), postoperative blood lactate (MD=0.45, 95%CI 0.15 to 0.75, P=0.004), postoperative electrolyte abnormalities (OR=5.94, 95%CI 3.50 to 10.09, P＜0.000 01), acute kidney injury (OR=1.92, 95%CI 1.34 to 2.75, P=0.000 4) and postoperative body temperature (MD=0.79, 95%CI 0.69 to 0.88, P＜0.000 01) were associated with postoperative delirium after surgery for Stanford type A aortic dissection. Conclusion The current evidence shows that age, male, drinking history, diabetes history, operation time, DHCA time, aortic occlusion time, cardiopulmonary bypass time, ICU stay, hospital stay, APACHEⅡ score, ventilation support time, hypoxemia and postoperative body temperature are risk factors for the postoperative delirium after surgery for Stanford type A aortic dissection. Oxygenation index, oxygen saturation, and hemoglobin number are protective factors for delirium after Stanford type A aortic dissection.

Objective To investigate the clinical and epidemiological characteristics of crayfish associated rhabdomyolysis syndrome in Baiyun District, Guangzhou, and explore the related factors, and to provide evidence for the prevention of crayfish rhabdomyolysis syndrome. Methods The cases of crawfish associated rhabdomyolysis syndrome were found through the foodborne disease surveillance and reporting system, and a field epidemiological investigation was carried out to analyze the clinical and epidemiological characteristics of the cases. Results A total of 25 cases of crayfish associated rhabdomyolysis syndrome occurred in 2020. The intake of crayfish of the cases ranged from 5 to 25, the incubation period was 1 to 9.5h, and the interval from onset to medical treatment was 0.17 to 9h. All the cases had muscle pain, and the content of creatine kinase (CK) in the cases increased to varying degrees (128-17851 U/L). Retrospective cohort analysis of 10 crayfish events found no correlation between the consumption of different parts of crayfish and the incidence of crayfish-related rhabdomyolysis syndrome. Conclusion The incidence of rhabdomyolysis syndrome reported in Baiyun District of Guangzhou is related to the consumption of crayfish, but the pathogenic factors need to be further studied. It is suggested to strengthen the supervision of crayfish breeding, transportation, sales, and processing to ensure the health of consumers.

Domestic scholars recognize that patients have a "pre-hepatic failure" before they progress to sub-acute and acute-on-chronic liver failure stage, which is also the golden window for effective clinical intervention, so early identification and intervention during this period can reduce the incidence and mortality of liver failure. The Guidelines for the Diagnosis and Treatment of Liver Failure (2018 Edition) issued by the Chinese Medical Association clearly defines the "pre-stage" of liver failure. And from the perspective of pathophysiological mechanism, the pre-hepatic failure corresponds to the stage of acute liver injury/acute decompensation, inflammation factor/ immunologic derangement. This article briefly introduces the research progress on substantive connotation and pathogenesis of pre-hepatic failure, and puts forward some problems to be explored in the future.

Objective: To study the effect of continuous nursing care on quality of life in patients with rheumatoid arthritis after discharge. Methods: Patients with rheumatoid arthritis who were admitted to hospital from August 2016 to August 2017 were selected as the study subjects. According to the random number table method, they were divided into the control group and the research group, and the lost cases were eliminated. There were 99 cases in the control group and 94 cases in the research group. The control group was given routine care, and the research group conducted continuous nursing care measures on the basis of the control group. The morning stiffness time, pain score, disease activity, patient health status and nursing satisfaction of the two groups were observed before and 6 weeks after discharge. Results: Six weeks after discharge, the morning stiffness time (23.76±12.76) min of the research group was significantly higher than that of the control group (38.22±14.53) min, the difference was statistically significant (t=3.865, P<0.05). Six weeks after discharge, the VAS (2.01±0.68) and HAQ (0.42±0.34) points of the research group were lower than those of the control group (4.17±1.30), (0.92±0.63) points, the difference was statistically significant (t=4.073, 3.916, P<0.05). The nursing satisfaction of the research group was 94.68%(89/94), and that of the control group was 78.79%(78/99), and the difference was statistically significant (χ²=9.416, P < 0.05). Conclusions The implementation of continuous care mode after discharge from patients with rheumatoid arthritis is beneficial to alleviate clinical symptoms such as morning stiffness and pain. Moreover, it can also improve patient health and quality of life, increase risk of disease progression, and care satisfaction is high which can help to protect the harmony between nurses and patients.