ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

OBJECTIVE: To investigate the distribution characteristics of polymorphonuclear neutrophil (PMN) in the lungs during the early stage of severe burns and the mechanism of neutrophil elastase (NE) promoting lung injury. METHODS: 6-8-week-old male C57BL/6J mice were selected for the experiments. A 30% total body surface area (TBSA) III degree burn mouse model was established (severe burn group); the Sham-injury group was treated with 37 centigrade water. In the sodium sivelestat intervention group (SV intervention group), NE competitive inhibitor, sivelestat, 100 mg/kg, was injected via tail vein immediately after injury, while other groups received an equal volume of saline. Ten mice were harvested from each group to observe survival for 72 hours. Respiratory function tests were tested at 0 (immediate), 3, 6, 12, and 24 hours after molding. hematoxylin-eosin (HE) and immunohistochemical staining were used to observe lung tissue structure, inflammatory changes and PMN infiltration. The PMN absolute count in mice lung tissue was detected buy flow cytometry. At 6, 12, and 24 hours after molding, PMN counts and the concentration of NE [enzyme linked immunosorbent assay (ELISA)] in peripheral blood plasma, lung tissue, and bronchoalveolar lavage fluid (BALF) were detected. RESULTS: (1) HE staining results showed that compared with the Sham-injury group, the lungs of mice in the severe burn group showed inflammatory changes and PMN infiltration, with more significant changes at 6 hours. Immunohistochemistry results also confirmed that the expression of NE protein released from PMN significantly increased after 6 hours of severe burn injury [(3.79±0.62)% vs. (0.18±0.05)%, t = 11.56, P < 0.01]. (2) Compared with the Sham-injury group, the number of PMN and the concentration of NE in the peripheral blood and lung tissues in the severe burn group were significantly increased (F values were 13.709, 55.350 and 29.890, 13.286, respectively, all P < 0.01), peaking at 6 hours [plasma PMN count (×10⁹/L): 2.92±1.01 vs. 0.92±0.29, lung tissue PMN absolute count (cells): 48 788.03±11 833.91 vs. 1 516.72±415.35, plasma NE (ng/L): 24 522.71±3 842.92 vs. 7 009.34±4 067.86, lung tissue NE (ng/L): 262 189.04±9 695.13 vs. 65 026.03± 16 016.31, all P < 0.01]. The number of PMN in the lung of severely burned mice was highly correlated with NE concentration (r = 0.892, P < 0.001). There was no significantly difference in the PMN absolute count in the BALF of mice between the Sham-injury group and severe burn group (F = 1.403, P > 0.05). The Sham-injury group and severe burn group contained a small amount of NE in the BALF, and the concentration of NE in the BALF of the severely burned 6 hours and 12 hours groups were significantly higher than those of the Sham-injury group (ng/L: 328.58±158.10, 415.30±240.89 vs. 61.95±15.80, both P < 0.05). (3) Kaplan-Meier survival curve showed that the 72-hour survival rate of mice in the SV intervention group was significantly higher than that in the severe burn group (100% vs. 10%, Log-Rank test: χ² = 19.12, P < 0.001). (4) Compared with the Sham-injury group, all lung function indices of the severe burn group decreased significantly. All lung function indices of SV intervention group improved gradually over time, which were significantly better than those of the severe burn group. (5) Compared with the Sham-injury group, the PMN absolute count in lung tissue and the concentration of NE in plasma and lung tissue were significantly higher in the SV intervention group (F values were 46.709, 3.535, 32.701, respectively, all P < 0.05), with a peak at 6 hours. Compared with the severe burn group, the SV intervention group had a higher PMN absolute count in lung tissue (cells: 8 870.80±7 013.89 vs. 25 974.92±22 240.8, P < 0.05), and higher plasma and lung tissue NE concentrations (ng/L: 14 955.94±3 944.41 vs. 21 972.75±4 573.05, 81 956.87±38 658.35 vs. 168 182.30±83 513.91, both P < 0.01) were significantly decreased. CONCLUSIONS In the early stage of severe burns, there is a significant infiltration of PMN into the lungs. The NE promotes lung injury in the early stage of severe burn, and improve lung injury by inhibiting the action of NE.
Animals ; Burns/metabolism* ; Leukocyte Elastase/metabolism* ; Male ; Mice, Inbred C57BL ; Mice ; Neutrophils/metabolism* ; Lung/metabolism* ; Disease Models, Animal ; Neutrophil Infiltration ; Lung Injury/metabolism* ; Glycine/analogs & derivatives* ; Sulfonamides

Objective To explore the application of regional cerebral oxygen saturation(rSO2)-bispectral index(BIS)monitoring anesthesia in children undergoing surgery for supracondylar fractures of the humerus.Methods A total of 60 children with supracondylar fractures of the humerus undergoing surgery in Department of Orthopedi,Jiangxi Provincial Children's Hospital were chosen and randomly number table method segmented into control group and observation group from January 2020 to December 2022,30 cases in each group.After anesthesia,children in observation group were carried out with rSO2-BIS monitoring,while children in control group were given routine anesthesia management.Results The dosage of propofol and long chain fat emulsion/remifentanil injection in observation group were significantly lower than those in control group(P＜0.05),while there was no difference in heart rate,blood oxygen saturation and mean arterial pressure at various time points during awakening(P＞0.05);The recovery rate of postoperative analgesics of observation group was lower than that of control group,and the extubation time of observation group was shorter than that of control group(P＜0.05);The incidence of postoperative adverse reactions and behaviors in observation group were lower than those in control group(P＜0.001).The dosage of propofol and long chain fat emulsion/remifentanil injection,as the independent risk factors inducing the occurrence of postoperative adverse reactions and adverse behaviors were proved by multivariate analysis.rSO2-BIS monitoring is a key factor in reducing postoperative adverse behaviors and reactions in pediatric patients(P＜0.05).Conclusion The use of rSO2-BIS monitoring during surgery for supracondylar fractures of the humerus in children can reduce the incidence rate of postoperative adverse behaviors and adverse reactions,thereby improving postoperative efficacy.

Objective:To analyze the clinical effect of low-frequency repetitive transcranial magnetic stimulation(rTMS)combined with neuromuscular joint facilitation(NJF)technique in improving the enhancement of muscle tone after stroke.Methods:From October 2020 to October 22,a total of 114 patients with increased muscle tone at lower limb during the recovery period of stroke who admitted to Beijing Rehabilitation hospital were selected,and they were randomly divided into the observation group(57 cases)and the control group(57 cases)according to the random number table method.The control group received routine rehabilitation treatment.The observation group added low-frequency rTMS and NJF training on the basis of the routine rehabilitation treatment.The differences of clinical efficacy and various indicators of muscle tone of lower limb before and after treatment between two groups were compared,which included modified Ashwonh score(MAS)scale,functional ambulation category(FAC)scale of the motor of lower limb,Fugl-Meyer motor function scale-Lower limbs(FMA-L),clinical spasmodic index(CSI),modified Barthel index(MBI)of activity ability of daily life,integrated electromyogram(IEMG)and root mean square(RMS)of tibialis anterior muscle of lower limb in electromyogram.Results:After intervention,29 cases appeared significant effect,and 23 cases appeared valid result,and 5 cases appeared invalid result in the observation group,and 20 cases appeared significant effect,and 20 cases appeared valid result,and 17 cases appeared invalid result in the control group.The total effective rate of the observation group was 91.23%,which was significantly higher than 70.18%of the control group,and the difference was statistically significant(x2=8.111,P<0.05).Before intervention,there was no statistically significant difference in each indicator between the two groups(P>0.05).The MAS score,CSI score,IEMG and RMS of two groups after intervention were significantly lower than those before intervention,while the FAC score,FMA-L score and MBI score were significantly higher than those before intervention,and the differences were significant(t=3.377,4.398,5.554,P<0.05),respectively.At the same time,the MAS score,CSI score,IEMG and RMS of the observation group were significantly higher than those of the control group,and the differences were statistically significant(t=11.160,9.625,16.993,8.095,P<0.05),respectively.Conclusion:The combined application of low-frequency rTMS and NJF training can significantly improve the enhancement of muscle tone after stroke,and effectively reduce the muscle tone of lower limb,and improve the motor function of lower limb and the degree of spasticity,and improve the activity ability of daily life.

Objective To construct an evidence-based prevention and management programme for peristomal moisture-associated skin damage in patients with enterostomy,and to evaluate its clinical effectiveness in improving the knowledge level of nurses and patients about peristomal moisture-associated skin damage in patients with enterostomy and reducing the incidence and severity of peristomal moisture-associated skin damage.Methods Through literature screening,evaluation,and summary,the best evidence for the prevention and management programme of peristomal moisture-associated skin damage in patients with enterostomy was summarized.From October 2021 to March 2022,based on the Ottawa research application model,review indicators were developed based on the best evidence for clinical review,identifying obstacles and promoting factors in evidence application,and developing action strategies to improve the evidence-based practice content for the prevention and management of peristomal moisture-associated skin damage in patients with enterostomy.From April to June 2022,evidence-based practice was conducted in the oncology surgery ward of a tertiary hospital in Anhui Province.The implementation rate of various review indicators by nurses,the knowledge level of peristomal moisture-associated skin damage of nurses and patients,and the incidence and severity of peristomal moisture-associated skin damage were compared before and after evidence-based practice.Results 46 cases were included before the evidence-based practice and 49 cases were included after the evidence-based practice.After evidence-based practice,the implementation rate of each review index was improved;the overall implementation rate increased from(0-66.67％)to(83.33％-100％);the score of the patient's knowledge questionnaire on peristomal moisture-associated skin damage was increased from(69.67±8.31)to(80.18±8.07).The score of the nurse's knowledge questionnaire on peristomal moisture-associated skin damage was increased from(79.83±5.97)to(88.28±5.43).At 4 weeks and 12 weeks of discharge,the incidence of peristomal moisture-associated skin damage was decreased,with a statistically significant difference(P＜0.05);the severity of peristomal moisture-associated skin damage was also significantly reduced,with a statistically significant difference(P＜0.05).Conclusion Conducting evidence-based practice for the prevention and management of peristomal moisture-associated skin damage can effectively improve the implementation rate of nurse review indicators,improve the knowledge level of nurses and patients with peristomal moisture-associated skin damage,and reduce the incidence and severity of peristomal moisture-associated skin damage in patients with enterostomy.

Objective To investigate the effect of agomelatine on the clinical efficacy in elderly patients with acute cerebral infarction(ACI)and comorbid anxiety-depression disorders by regu-lating serum neurotransmitters and nerve cytokines.Methods A total of 160 elderly ACI patients with anxiety and depression symptoms admitted in Pingxiang Second People's Hospital from June 2020 to December 2023 were enrolled in this study.All of them received thrombolysis or interven-tional therapy,and then were randomly divided into control and observation groups,with 80 patients in each group.The control group received conventional psychological intervention,while the observation group was given additional oral administration of agomelatine.Cognitive function,neurological function,neurotransmitters and neuronal cytokines,anxiety and depression scores,sleep quality,quality of life,daily activity ability and adverse reactions were compared between the two groups.Results After intervention,Mini Mental State Examination(MMSE)scores,levels of neuropeptide Y(NPY),5-hydroxytryptamine(5-HT),norepinephrine(NE),dopamine and brain-derived neurotrophic factor(BDNF),36-item Brief Health Questionnaire(SF-36)score,and Bar-thel index scale score were significantly higher in both 2 groups when compared with above indicators before the intervention(P＜0.01).And the MMSE score,NPY,5-HT,NE,dopamine and BDNF levels,SF-36 score and Barthel index scale score were obviously higher in the observa-tion group than the control group(P＜0.01).Both groups obtained notably lower NIHSS score,S100 calcium binding protein B(S100B)and myelin basic protein(MBP)levels,Hamilton Anxiety Rating Scale(HAMA)score,and Hamilton Depression Rating Scale 17(H AMD-17)score and Pittsburgh Sleep Quality Index(PSQI)score after intervention(P＜0.01).And the NIHSS score,S100B and MBP levels,HAMA score,HAMD-17 score,and PSQI score were statistically lower in the observation group than the control group(P＜0.01).During the treatment process,no signifi-cant difference was observed in the incidence of total adverse reactions between the two groups(3.75％vs 6.25％,x2=0.526,P=0.468).Conclusion When agomelatine tablets are indicated for ACI patients with concomitant anxiety-depression disorders,they can effectively rehabilitate cog-nitive function,enhance neurological function,improve sleep quality and quality of life,optimize activities of daily living,eliminate negative emotions,and correct the expression of neurotransmit-ters and neurotrophic factors.