Objective:To evaluate the effect of age factor on the sedative potency of ciprofol.Methods:In this prospective study, patients of either sex, aged 40-80 yr, undergoing elective surgery under general anesthesia at the First Affiliated Hospital of Zhengzhou University, were selected and divided into middle-aged group (40-<65 yr) and elderly group (65-80 yr) based on their age. Effective sedation was defined as the Modified Observer′s Assessment of Alertness/Sedation scale score ≤1 and the bispectral index value ≤60 within 3 min following ciprofol administration. The initial dose of ciprofol was 0.4 mg/kg. The dose of ciprofol was determined by using the modified Dixon′s up-and-down method (increment or decrement of 0.04 mg/kg). The experiment was terminated after observing 8 transitions from effective sedation to ineffective sedation, starting from the initial transition event. The probit method was used to determine the median effective dose (ED 50) and 95% confidence interval of ciprofol for sedation. Results:A total of 61 patients was finally included in this study, with 35 in middle-aged group and 26 in elderly group. The ED 50 of ciprofol (95% confidence interval) was 0.296 (0.206-0.359) mg/kg in middle-aged group and 0.224 (0.185-0.257) mg/kg in elderly group. The ED 50 of ciprofol was significantly higher in middle-aged group than in elderly group ( u=181.00, P<0.001). Conclusions:Age can affect the sedative potency of propofol, with enhanced potency observed in elderly patients than in middle-aged patients.

BACKGROUND:According to existing clinical studies,vertebroplasty treatment with both the external pedicle approach and the pedicle approach can improve the pain and quality of life of patients with spinal compression fractures.Compared with the pedicle approach,the external pedicle approach has a freer puncture angle,and good bone cement dispersion effect can be obtained by adjusting the puncture angle. OBJECTIVE:To compare the impact of vertebroplasty through individualized unilateral external pedicle approach and bilateral pedicle approach on the treatment of spinal compression fractures by quantifying the dispersion effect of bone cement. METHODS:A total of 80 patients with thoracolumbar compression fracture were divided into two groups by random number table method.The bilateral pedicle group(n=40)underwent vertebroplasty through a bilateral pedicle approach,while the unilateral external pedicle group(n=40)underwent individualized vertebroplasty through a unilateral external pedicle approach.Anteroposterior and lateral X-rays of the affected vertebrae from two groups of patients were photographed to assess effect and type of bone cement dispersion within 3 days after surgery.Visual analog scale score,tenderness threshold around fracture,and Oswestry dysfunction index were assessed before,1,7 days,and 1 month after surgery. RESULTS AND CONCLUSION:(1)Dispersion effect of bone cement in unilateral external pedicle group was better than that in bilateral pedicle group(P<0.001),and the amount of bone cement perfusion was higher than that in bilateral pedicle group(P<0.001).In the bilateral pedicle group,the bone cement dispersion types were mainly concentrated in type Ⅰ and type Ⅲ,while in the unilateral external pedicle group,the bone cement dispersion types were mainly concentrated in type I and type Ⅱ,and there was a significant difference in bone cement dispersion types between the two groups(P<0.001).(2)Postoperative visual analog scale scores and Oswestry disability index of both groups were lower than those before surgery(P<0.001),and postoperative tenderness threshold around fracture showed a trend of decreasing first and then increasing.At the same time point after treatment,there were no significant differences in visual analog scale score,Oswestry disability index,and tenderness threshold around fracture between the two groups(P>0.05).(3)The results indicate that individualized vertebroplasty via unilateral external pedicle approach can achieve better bone cement dispersion,and the treatment effect is consistent with the vertebroplasty via classical bilateral pedicle approach.

Objective:To evaluate the effect of age factor on the sedative potency of ciprofol.Methods:In this prospective study, patients of either sex, aged 40-80 yr, undergoing elective surgery under general anesthesia at the First Affiliated Hospital of Zhengzhou University, were selected and divided into middle-aged group (40-<65 yr) and elderly group (65-80 yr) based on their age. Effective sedation was defined as the Modified Observer′s Assessment of Alertness/Sedation scale score ≤1 and the bispectral index value ≤60 within 3 min following ciprofol administration. The initial dose of ciprofol was 0.4 mg/kg. The dose of ciprofol was determined by using the modified Dixon′s up-and-down method (increment or decrement of 0.04 mg/kg). The experiment was terminated after observing 8 transitions from effective sedation to ineffective sedation, starting from the initial transition event. The probit method was used to determine the median effective dose (ED 50) and 95% confidence interval of ciprofol for sedation. Results:A total of 61 patients was finally included in this study, with 35 in middle-aged group and 26 in elderly group. The ED 50 of ciprofol (95% confidence interval) was 0.296 (0.206-0.359) mg/kg in middle-aged group and 0.224 (0.185-0.257) mg/kg in elderly group. The ED 50 of ciprofol was significantly higher in middle-aged group than in elderly group ( u=181.00, P<0.001). Conclusions:Age can affect the sedative potency of propofol, with enhanced potency observed in elderly patients than in middle-aged patients.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Background::High sodium intake is an important risk factor for hypertension and cardiovascular disease. However, the association between gut microbiota composition and metabolomic profiles with dietary sodium intake and blood pressure (BP) is not well-understood. The metabolome, microbiome, and dietary salt intervention (MetaSalt) study aimed to investigate microbial and metabolomic profiles related to dietary sodium intake and BP regulation.Methods::This family-based intervention study was conducted in four communities across three provinces in rural northern China in 2019. Probands with untreated prehypertension or stage-1 hypertension were identified through community-based BP screening, and family members including siblings, offspring, spouses, and parents were subsequently included. All participants participated in a 3-day baseline examination with usual diet consumption, followed by a 10-day low-salt diet (3 g/d of salt or 51.3 mmol/d of sodium) and a 10-day high-salt diet (18 g/d of salt or 307.8 mmol/d of sodium). Differences in mean BP levels were compared according to the intervention phases using a paired Student's t-test.Results::A total of 528 participants were included in this study, with a mean age of 48.1 years, 36.7% of whom were male, 76.8% had a middle school (69.7%) or higher (7.1%) diploma, 23.4% had a history of smoking, and 24.4% were current drinkers. The mean arterial pressure at baseline was 97.2 ± 10.5 mm Hg for all participants, and significantly decreased during the low-salt intervention (93.8 ± 9.3, P < 0.0001) and subsequently increased during the high-salt intervention (96.4 ± 10.0, P < 0.0001). Conclusions::Our dietary salt intervention study has successfully recruited participants and will facilitate to evaluate the effects of gut microbiota and metabolites on BP regulation in response to sodium burden, which will provide important evidence for investigating the underlying mechanisms in the development of hypertension and subsequent cardiovascular diseases.Trial registration::The study was registered in the Chinese Clinical Trial Registry database (ChiCTR1900025171).

Background::High sodium intake is an important risk factor for hypertension and cardiovascular disease. However, the association between gut microbiota composition and metabolomic profiles with dietary sodium intake and blood pressure (BP) is not well-understood. The metabolome, microbiome, and dietary salt intervention (MetaSalt) study aimed to investigate microbial and metabolomic profiles related to dietary sodium intake and BP regulation.Methods::This family-based intervention study was conducted in four communities across three provinces in rural northern China in 2019. Probands with untreated prehypertension or stage-1 hypertension were identified through community-based BP screening, and family members including siblings, offspring, spouses, and parents were subsequently included. All participants participated in a 3-day baseline examination with usual diet consumption, followed by a 10-day low-salt diet (3 g/d of salt or 51.3 mmol/d of sodium) and a 10-day high-salt diet (18 g/d of salt or 307.8 mmol/d of sodium). Differences in mean BP levels were compared according to the intervention phases using a paired Student's t-test.Results::A total of 528 participants were included in this study, with a mean age of 48.1 years, 36.7% of whom were male, 76.8% had a middle school (69.7%) or higher (7.1%) diploma, 23.4% had a history of smoking, and 24.4% were current drinkers. The mean arterial pressure at baseline was 97.2 ± 10.5 mm Hg for all participants, and significantly decreased during the low-salt intervention (93.8 ± 9.3, P < 0.0001) and subsequently increased during the high-salt intervention (96.4 ± 10.0, P < 0.0001). Conclusions::Our dietary salt intervention study has successfully recruited participants and will facilitate to evaluate the effects of gut microbiota and metabolites on BP regulation in response to sodium burden, which will provide important evidence for investigating the underlying mechanisms in the development of hypertension and subsequent cardiovascular diseases.Trial registration::The study was registered in the Chinese Clinical Trial Registry database (ChiCTR1900025171).

Objective: To explore the relationship between childhood abuse and cyberbullying among college students and to provide theoretical support for early intervention of cyberbullying among college students. Methods: A total of 3 850 sophomores and juniors from 6 universities in Shanxi Province, randomly selected by stratified cluster sampling method, were investigated by using the Questionnaire on Cyberbullying and the Chinese Version of the Child Abuse Questionnaire. Results: Male students reported higher rates of sexual abuse, emotional neglect and physical neglect than female students(χ2=5.22, 4.39, 7.53 P<0.05). The child abuse report rate of college students whose parents divorced was higher than that of those whose parents were not divorced(χ2=86.80, 134.06, 130.18, 175.64, 118.46，P<0.05). In addition to physical neglect, childhood abuse rate of only children was higher than that of non-only children, with statistically significant differences(χ2=9.44, 12.44, 21.18, 21.26, all P<0.05). The scores of all factors and total scores of cyberbullying implemented by male students were higher than those by female students(t=9.35, 5.59, 5.83, 7.57，P<0.05); the scores of all factors and total scores of cyberbullying implemented by only-child students were higher than those by non-only-child students(t=2.79, 3.74, 4.78, 4.40，P<0.05); the scores of all factors and total scores of cyberbullying implemented by students whose parents were divorced were higher than those by students whose parents were not divorced, with statistically significant differences(t=6.99,6.78, 8.04，11.33, P<0.05). Multiple linear regression model showed that there was a positive correlation between the childhood abuse of college students and the implementation of cyberbullying, and regression coefficient differences of all factors were statistically significant(β=0.10, 0.11, 0.05, 10.08,0.06, P<0.05). Conclusion Childhood abuse experiences increase the risk of college students practicing cyberbullying.

Objective:To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China.Methods:Two phase Markov models were constructed for a hypothetical cohort of patients aged 45 with stage Ⅱ breast cancer. The first phase modelled costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC×4, febrile neutropenia (FN) risk>20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity analysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4.1)]. Second phase modelled the long term survival which was link with the relative dose intensity (RDI) [mortality hazard ratio ( HR) of RDI < 85% vs ≥85%, 1.45 (1.00-2.32)]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results:Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79 146.3 RMB and 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (18, 000 RMB) recommended by the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-CSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. And the lower the mortality HR of RDI<85% vs ≥85% is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. Conclusion:Although the cost of PP PEG-rhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to be a cost-effective alternative to PP rhG-CSF and no prophylaxis in patients with early stage breast cancer whose FN risks are more than 20% in China.

Objective:To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China.Methods:Two phase Markov models were constructed for a hypothetical cohort of patients aged 45 with stage Ⅱ breast cancer. The first phase modelled costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC×4, febrile neutropenia (FN) risk>20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity analysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4.1)]. Second phase modelled the long term survival which was link with the relative dose intensity (RDI) [mortality hazard ratio ( HR) of RDI < 85% vs ≥85%, 1.45 (1.00-2.32)]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results:Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79 146.3 RMB and 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (18, 000 RMB) recommended by the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-CSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. And the lower the mortality HR of RDI<85% vs ≥85% is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. Conclusion:Although the cost of PP PEG-rhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to be a cost-effective alternative to PP rhG-CSF and no prophylaxis in patients with early stage breast cancer whose FN risks are more than 20% in China.

Objective To evaluate the effect of dexmedetomidine on the long-term anxiety state after sevoflurane anesthesia in neonatal rats and the role of different central subtypes of α2 receptors.Methods A total of 216 clean-grade healthy male Sprague-Dawley rats,aged 4-6 days,weighing 8-15 g,were divided into 6 groups (n =36 each) using a random number table method:control group (group C),sevoflurane group (group S),dexmedetomidine + sevoflurane group (group D+S),dexmedetomidine + α2 receptor antagonist atipamezole + sevoflurane group (group D+A+S),dexmedetomidine + α2A receptor antagonist BRL44408 + sevoflurane group (group D+B+S),and dexmedetomidine + α2C receptor antagonist JP1302 + sevoflurane group (group D+J+S).Anesthesia was induced by inhaling 6％ sevoflurane for 3 min and maintained by inhaling 2.1％ sevoflurane for 6 h.At 30 min before anesthesia induction,dexmedetomidine 25 μg/kg was intraperitoneally injected in group D+S,dexmedetomidine 25 μg/kg and atipamezole 250 μg/kg were intraperitoneally injected in group D + A + S,dexmedetomidine and α2A receptor antagonist BRL44408 1.5 mg/kg were intraperitoneally injected in group D+B+S,and dexmedetomidine 25 μg/kg and α2C receptor antagonist JP1302 3 mg/kgwere intraperitoneally injected in group D+J+S.Twelve rats in each group were randomly selected and sacrificed after the end of anesthesia,blood samples were collected for blood gas analysis,and the serum corticosterone concentration was measured by enzyme-linked immunosorbent assay.The elevated plus maze was performed when the left rats in each group were 60 days old,and 12 rats were selected when the they were 80 days old to perform the restraint stress test.Results Compared with group C,the percentage of time of staying at the open arm was significantly decreased,the total motion distance was shortened,and the serum corticosterone concentration was increased after the end of anesthesia and during the restraint stress test in S,D+A+S and D+B+S groups (P＜0.05),and no significant change was found in the parameters mentioned above in D+S and D+J+S groups (P＞0.05).Compared with group S,the percentage of time of staying at the open arm was significantly increased,the total motion distance was prolonged,and the serum corticosterone concentration was decreased after the end of anesthesia and during the restraint stress test in group D+S and group D+J+S (P＜0.05),and no significant change was found in the parameters mentioned above in group D+A+S and group D+B+S (P ＞0.05).Compared with group D+S,the percentage of time of staying at the open arm was significantly decreased,the total motion distance was shortened,and the serum corticosterone concentration was increased after the end of anesthesia and during the restraint stress test in D+A+S and D+B+S groups (P＜0.05),and no significant change was found in the parameters mentioned above in group D+J +S (P＞ 0.05).Conclusion Dexmedetomidine can reduce the long-term anxiety state after sevoflurane anesthesia in neonatal rats,and the mechanism may be related to activating central α2A receptors and improving hypothalamic-pituitary-adrenocortical axis hyperfunction.