Objective To investigate the main pharmacological basis and mechanism of action of Guhuaisi Kangfu Pill(GHSKF)in the treatment of steroid-induced osteonecrosis of the femoral head(SONFH).Methods The active constituents and targets of GHSKF were screened by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and other databases.The speculative targets of SONFH were screened out based on GeneCards and Online Mendelian Inheritance in Man(OMIM)databases.The gene modules and hub genes of SONFH were identified using a weighted gene co-expression network analysis(WGCNA).The intersection of the two targets and the result of WGCNA was taken to obtain the potential targets of GHSKF for the treatment of SONFH.The key active constituents were screened with the"active constituent-target"network,which was constructed by the Cytoscape software.Then,the STRING database was used to construct the protein interaction network to screen the key targets.The Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of key targets was performed,and the relationship between key active constituent,key targets and key signaling pathways was explored.Finally,the molecular docking between key active constituents and key targets was verified.In addition,the SONFH rat model was used for experimental verification.Results A total of 146 compounds and the corresponding 346 targets were identified based on the TCMSP database.A total of 4 187 targets of SONFH were obtained based on GeneCards and OMIM databases.In addition,twelve gene modules and 2 556 hub genes of SONFH were screened out based on WGCNA.Quercetin,luteolin and kaempferol were key active ingredients for the treatment of SONFH.Various signaling pathways such as PI3K/AKT were involved.Molecular docking showed the key active ingredients had good binding activity with the key targets.The results of animal experiments demonstrated that GHSKF could improve bone biological alterations by up-regulating AKT1,PI3K,RUNX2,and down-regulating the expression of Caspase-3 and IL-6(P＜0.01),which verified some results of the network pharmacology prediction.Conclusion We analyzed the potential mechanism of action of GHSKF for the treatment of SONFH using network pharmacology and animal experiments,which may provide a reference for further research on its pharmacological basis and targets.

ObjectiveTo explore the therapeutic mechanism of Bushen Huoxue prescription from the perspective of bone metabolism by observing the clinical efficacy of this prescription in treating femoral head necrosis （ONFH， syndrome of liver and kidney deficiency） and its influences on bone metabolism indexes： N-terminal propeptide （PINP） and β-collagen degradation product （β-CTX）. MethodSixty-six ONFH patients with the syndrome of liver and kidney deficiency in Zhengzhou Traditional Chinese Medicine Hospital of Orthopedics from December 2021 to September 2022 were selected. The patients were randomized into an experimental group and a control group by the parallel control method， with 33 patients in each group. The experimental group received Bushen Huoxue prescription orally， while the control group received Xianlinggubao Capsules orally， with a treatment cycle of 6 months. The visual analogue scale （VAS） score， Harris score， Association Research Circulation Osseous （ARCO） staging， imaging changes， quantitative scores of TCM symptoms， and serum levels of PINP and β-CTX were determined before and after treatment. The occurrence of adverse events and reactions was recorded. ResultThe total response rate in the experimental group was 83.87% （26/31）， which was higher than that （68.75%， 22/32） in the control group （Z=-2.096， P<0.05）. After treatment， the single and total scores of TCM symptoms， VAS score， and β-CTX level decreased in the two groups （P<0.05）. Moreover， the decreases in the scores of hip pain， lower limb mobility， soreness of waist and knees， and lower limb flaccidity， total score of TCM symptoms， VAS score， and β-CTX level in the experimental were larger than those in the control group （P<0.05）. After treatment， the imaging results showed no significant improvement in the two groups. The Harris score and PINP level in both groups increased after treatment （P<0.05）， and the increases were more obvious in the experimental group than in the control group （P<0.05）. No serious adverse event or adverse reaction appeared during the observation period. ConclusionBushen Huoxue prescription can relieve pain and TCM symptoms and improve the hip joint function in treating ONFH patients with the syndrome of liver and kidney deficiency. It can inhibit the development of ONFH， increase PINP， and decrease β-CTX. No obvious side effect appears during the clinical observation period， which shows that Bushen Huoxue prescription has good safety.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective To investigate the effects of different concentrations of morphine in combination with ropivacaine on proliferation,migration,invasion and cell cycle in MDA-MB-231 breast cancer cells.Methods MDA-MB-231 breast cancer cells were inoculated on the culture plate for 24h and randomly divided into 8 groups:Control group(C),ropivacaine 400μg/ml group(R),morphine 3μg/ml group(LM),morphine 30μg/ml group(MM),morphine 300μg/ml group(HM),ropivacaine 400μg/ml group+ morphine 3μg/ml group(R+LM),ropivacaine 400μg/ml+ morphine 30μg/ml group(R+MM),and ropivacaine 400μg/ml+ morphine 300μg/ml group(R+HM).After treaments of MDA-MB-231 breast cancer cells for 24h,these proliferation,migration,invasion and cell cycle were evaluated.Results When using morphine alone,the proliferation inhibitive effect was positively correlated with the concentration of morphine.The proliferation was significantly inhibited by morphine of LM,MM,HM group(P<0.05).When using ropivacaine alone,the proliferation was significantly inhibited(P<0.05).When using morphine combined with ropivacaine,the high concentration morphine group has a synergistic effect with ropivacaine group on proliferation inhibition(P<0.05).When using morphine alone,the migration rate decreases sequentially with the increase of morphine concentration.The migration rate was significantly inhibited by morphine of LM,MM,HM group(P<0.05).When using ropivacaine alone,the migration rate was inhibited(P<0.05).When using morphine combined with ropivacaine,the low and medium concentration morphine group have a synergistic effect with ropivacaine group on migration rate(P<0.05).When using morphine alone,the number of cell invasion was decreased with the concentration of morphine increasing(P<0.05).The MM and HM groups inhibited cell invasion ability.When using ropivacaine alone,the invasiveness of cells was also inhibited(P<0.05).When using morphine combined with ropivacaine,the medium and high concentration morphine groups have a synergistic effect with ropivacaine group on inhibiting cell invasion ability(P<0.05).When using morphine alone,the cell cycle progression was inhibited into G2/M Phase(P<0.05).When using ropivacaine alone,the cell cycle progression was inhibited into G2/M phase(P<0.05).The combination of low concentration morphine and ropivacaine has synergistic effect on arresting at G0/G1 and S phase(P<0.05).Conclusion Morphine combined with ropivacaine inhibits the Proliferation,migration and invasion of MDA-MB-231 breast cancer cells in a dose-dependent manner.

Objective:To investigate the application value of laparoscopic-assisted total liver transplantation.Methods:The retrospective and descriptive study was conducted. The clinical data of 9 pairs of donors and recipients who underwent laparoscopic-assisted total liver transplanta-tion in People′s Hospital of Guangxi Zhuang Autonomous Region from January to April 2024 were collected. Of the donors, there were 8 males and 1 female, aged (39±18)years and with body mass index (BMI) of (20±4)kg/m 2. Of the recipients, there were 7 males and 2 females, aged (41±13)years and with BMI of (24±4)kg/m 2. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers. Results:(1) Surgical conditions. Of the 9 recipients, 7 recipients underwent laparoscopic-assisted total liver transplantation successfully, 1 recipient with severe portal hypertension converted to open surgery with reverse L-shaped incision due to the hemorrhage during the dissection of the first hepatic portal after completing liver mobilization under laparoscopy, and 1 recipient underwent trans-umbilical extension incision through the middle of the epigastric region due to the limited space for operation in the implantation of the donor liver. The total operation time for 7 recipients who successfully underwent laparoscopic-assisted total liver transplantation was (648±31)minutes, with a time of anhepatic phase of (57±5)minutes, the volume of intraoperative blood loss of (1 322±627)mL, the donor liver mass of (1 195±232)g, and the ratio of donor liver mass to recipient body mass of 1.86%±0.42%. The operation time for laparoscopic liver dissection and porta hepatis dissection in 8 recipients during surgery was (212±35)minutes. (2) Postoperative conditions. All 9 recipients recovered smoothly after surgery, without any vascular or biliary related complications, and the surgical incision recovered well. The duration of postoperative hospital stay of 7 recipients who successfully underwent laparoscopic-assisted total liver transplantation was (14.2±2.0)days. (3) Follow-up. All 9 recipients were followed up for 3 months after surgery. During the follow-up period, there was no vascular or bile duct related complication.Conclusion:Laparoscopic-assisted total liver transplantation can be applied to recipients who meet surgical conditions and achieve good short-term clinical efficacy.

Objective:To investigate the application value of laparoscopic-assisted total liver transplantation.Methods:The retrospective and descriptive study was conducted. The clinical data of 9 pairs of donors and recipients who underwent laparoscopic-assisted total liver transplanta-tion in People′s Hospital of Guangxi Zhuang Autonomous Region from January to April 2024 were collected. Of the donors, there were 8 males and 1 female, aged (39±18)years and with body mass index (BMI) of (20±4)kg/m 2. Of the recipients, there were 7 males and 2 females, aged (41±13)years and with BMI of (24±4)kg/m 2. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers. Results:(1) Surgical conditions. Of the 9 recipients, 7 recipients underwent laparoscopic-assisted total liver transplantation successfully, 1 recipient with severe portal hypertension converted to open surgery with reverse L-shaped incision due to the hemorrhage during the dissection of the first hepatic portal after completing liver mobilization under laparoscopy, and 1 recipient underwent trans-umbilical extension incision through the middle of the epigastric region due to the limited space for operation in the implantation of the donor liver. The total operation time for 7 recipients who successfully underwent laparoscopic-assisted total liver transplantation was (648±31)minutes, with a time of anhepatic phase of (57±5)minutes, the volume of intraoperative blood loss of (1 322±627)mL, the donor liver mass of (1 195±232)g, and the ratio of donor liver mass to recipient body mass of 1.86%±0.42%. The operation time for laparoscopic liver dissection and porta hepatis dissection in 8 recipients during surgery was (212±35)minutes. (2) Postoperative conditions. All 9 recipients recovered smoothly after surgery, without any vascular or biliary related complications, and the surgical incision recovered well. The duration of postoperative hospital stay of 7 recipients who successfully underwent laparoscopic-assisted total liver transplantation was (14.2±2.0)days. (3) Follow-up. All 9 recipients were followed up for 3 months after surgery. During the follow-up period, there was no vascular or bile duct related complication.Conclusion:Laparoscopic-assisted total liver transplantation can be applied to recipients who meet surgical conditions and achieve good short-term clinical efficacy.

Objective:To explore effects of the specialist nurse training program of based on the context, input, process, product (CIPP) evaluation model in the training of junior nurses in the Department of Otolaryngology.Methods:From April 2018 to May 2020, convenience sampling method was used to select 80 specialist nurses who received training in the Shandong ENT Hospital as research objects. A total of 40 nurses who received traditional training from April 2018 to March 2019 were divided into a control group. From April 2019 to May 2020, 40 nurses who were trained in a specialist nurse training program based on the CIPP evaluation model were divided into observation groups. This study compared nurses' core competence and training qualification rate.Results:After training, the core competence score of observation group was higher than that of control group, and the difference was statistically significant ( P<0.05) . The training qualification rate of observation group and control group was 92.50% (37/40) and 70.00% (28/40) respectively, also with a statistical difference ( P<0.05) . Conclusions:The training program for specialist nurses based on the CIPP evaluation model can improve the theoretical knowledge and practical ability of nurses, and then improve the quality of clinical care, and promote the long-term development of the hospital, which is worthy of promotion.

Objective: To analyze the extubation indications of tracheotomy patients with severe neuropathy by Meta-analysis in order to determine the effective indication parameters for successful extubation. Methods: The literatures in databases including China National Knowledge Infrastructure (CNKI), Wanfang, VIP, Web of Science, PubMed and Cochrane Library were retrieved from their establishment to April 2019. The literatures were case-control studies, cohort studies, randomized controlled trials (RCTs) or surveys related to indication parameters for successful extubation in patients with severe neuropathy. Two researchers identified and extracted literatures and data independently. The quality of literatures was assessed by the Newcastle-Ottawa scale (NOS). Meta-analysis was performed by RevMan 5.3 software. The stability of the results were evaluated by assessing the statistical models (the fixed effects model or the random effects model) and literatures quality (inferior or superior), and by sensitivity analysis. The publication bias of literatures was assessed by funnel plot. Results: Eleven studies involving 1 357 participants were enrolled, and the rate of successful extubation was 46.7%-97.5%. Nine studies defined successful extubation as no need of re-intubation, and other two did not explain. All studies were high quality research, with NOS score of 6-8. Meta-analysis showed that the correlation between the level of consciousness [Glasgow coma score (GCS) ≥ 8 vs. < 8: odds ratio (OR) = 3.34, 95% confidence interval (95%CI) was 2.22-5.03, P < 0.001], the amount of tracheal secretions (less vs. more: OR = 13.07, 95%CI was 5.64-30.32, P < 0.001), cough reflex (with vs. without: OR = 14.33, 95%CI was 6.36-32.28, P < 0.001), swallowing function (good vs. bad: adjusted OR = 18.56, 95%CI was 8.16-42.21, P < 0.001) and successful extubation was statistically significant, and the correlation between the pulmonary infection (with vs. without: adjusted OR = 1.94, 95%CI was 0.87-4.35, P = 0.11), oxygen saturation (≥ 0.95 vs. < 0.95: OR = 2.34, 95%CI was 1.11-4.91, P = 0.12), tolerance of tube plugging (good vs. bad: OR = 2.12, 95%CI was 0.67-6.71, P = 0.20), method of tube drawing (gradually vs. abruptly: OR = 0.99, 95%CI was 0.95-1.04, P = 0.93) and successful extubation was not statistically significant. Sensitivity analysis showed that the results were stable. Funnel plot showed that the studies distributed in both sides of the funnel symmetrically, indicating the publication bias of literatures was small. Conclusion The effective indication of extubation is consciousness level (GCS score ≥ 8), less secretion, cough reflex and good swallowing function.

OBJECTIVE: To analyze the extubation indications of tracheotomy patients with severe neuropathy by Meta-analysis in order to determine the effective indication parameters for successful extubation. METHODS: The literatures in databases including China National Knowledge Infrastructure (CNKI), Wanfang, VIP, Web of Science, PubMed and Cochrane Library were retrieved from their establishment to April 2019. The literatures were case-control studies, cohort studies, randomized controlled trials (RCTs) or surveys related to indication parameters for successful extubation in patients with severe neuropathy. Two researchers identified and extracted literatures and data independently. The quality of literatures was assessed by the Newcastle-Ottawa scale (NOS). Meta-analysis was performed by RevMan 5.3 software. The stability of the results were evaluated by assessing the statistical models (the fixed effects model or the random effects model) and literatures quality (inferior or superior), and by sensitivity analysis. The publication bias of literatures was assessed by funnel plot. RESULTS: Eleven studies involving 1 357 participants were enrolled, and the rate of successful extubation was 46.7%-97.5%. Nine studies defined successful extubation as no need of re-intubation, and other two did not explain. All studies were high quality research, with NOS score of 6-8. Meta-analysis showed that the correlation between the level of consciousness [Glasgow coma score (GCS) ≥ 8 vs. < 8: odds ratio (OR) = 3.34, 95% confidence interval (95%CI) was 2.22-5.03, P < 0.001], the amount of tracheal secretions (less vs. more: OR = 13.07, 95%CI was 5.64-30.32, P < 0.001), cough reflex (with vs. without: OR = 14.33, 95%CI was 6.36-32.28, P < 0.001), swallowing function (good vs. bad: adjusted OR = 18.56,95%CI was 8.16-42.21, P < 0.001) and successful extubation was statistically significant, and the correlation between the pulmonary infection (with vs. without: adjusted OR = 1.94, 95%CI was 0.87-4.35, P = 0.11), oxygen saturation (≥ 0.95 vs. < 0.95: OR = 2.34, 95%CI was 1.11-4.91, P = 0.12), tolerance of tube plugging (good vs. bad: OR = 2.12, 95%CI was 0.67-6.71, P = 0.20), method of tube drawing (gradually vs. abruptly: OR = 0.99, 95%CI was 0.95-1.04, P = 0.93) and successful extubation was not statistically significant. Sensitivity analysis showed that the results were stable. Funnel plot showed that the studies distributed in both sides of the funnel symmetrically, indicating the publication bias of literatures was small. CONCLUSIONS The effective indication of extubation is consciousness level (GCS score ≥ 8), less secretion, cough reflex and good swallowing function.
Airway Extubation ; China ; Cohort Studies ; Humans ; Odds Ratio ; Tracheostomy

Objective To compare the difference in radiotherapy dose caused by different ways of adding bolus.Methods A total of 20 patients who needed to receive postmastectomy chest wall irradiation from October to December on 2014 were selected.Each patient underwent two CT scans;CT-1 was to perform CT scan directly without bolus, and CT-2 was to perform CT scan after adding bolus to the body surface.An equivalent bolus was added for CT-1 in the radiotherapy planning system, and Plan-1, which met the clinical requirements, was performed.Then Plan-1 was put on CT-2 through image fusion and plan verification to develop Plan-2, which was to develop plans with equivalent boluses at other times and perform radiotherapy with a bolus added to the surface of the body.At last, CT-2 was used to perform radiotherapy Plan-3, which met the clinical requirements.The paired t-test was used for comparison of clinical data between any two plans with SPSS 19.0.Results The V20 of the whole lung, V20 of the diseased lung, V30 of the heart, and Dmax of the healthy breast showed no significant differences across the three plans (P=0.074-0.871).The V50 , V55 , conformity index, and homogeneity index of the planning target showed significant differences across the three plans, and the total number of monitor units showed a significant difference between Plan-1 and Plan-2(P=0.002-0.049).The dose distribution in the target volume and the number of monitor units in each radiation field also showed significant differences.Conclusions When the equivalent bolus is added to the body surface before CT scan, such a plan can accurately reflect the dose distribution of the planning target and the dose to organs at risk.