OBJECTIVE To study the pharmacokinetic changes in the plasma and cerebrospinal fluid of bronchial asthma model rats after the complication of Ephedra sinica and Prunus armeniaca. METHODS SD male rats were randomly divided into blank group， model group， E. sinica group （12 g/kg， calculated by raw drug， similarly hereinafter）， P. armeniaca group （6 g/kg） and E. sinica-P. armeniaca drug-pair group （12 g/kg of E. sinica+6 g/kg of P. armeniaca）， with 6 rats in each group. Except for the blank group， the bronchial asthma model was induced by spraying rats in each group with an equal volume mixture of 2% acetylcholine chloride and 0.4% histamine phosphate， once a day， for 7 d. One hour before modeling every time， rats in each group were gavaged with the corresponding drug/normal saline， once a day， for 7 d. After the final administration and provocation of asthma， blood and cerebrospinal fluid collection were performed at different time points. The plasma and cerebrospinal fluid samples were pre-treated （with geranylgeranyl as the internal standard）， and the mass concentrations of ephedrine/pseudoephedrine， methyl ephedrine and amygdalin in both samples were determined by liquid chromatography-tandem mass spectrometry. DAS 2.0 pharmacokinetic software was used to determine the main pharmacokinetic parameters through the non-atrial chamber model and to compare the changes of the pharmacokinetic parameters before and after the combination of the two drugs. RESULTS Compared with E. sinica group， cmax and AUC0-21.33 h （or AUC0-10.67 h） of ephedrine/pseudoephedrine and methyl ephedrine in the plasma and cerebrospinal fluid of rats were significantly reduced in E. sinica-P. armeniaca drug-pair group， while CLZ/F and VZ/F were significantly increased （P＜0.05 or P＜0.01）； tmax of methyl ephedrine in the cerebrospinal fluid was significantly shortened （P＜ 0.05）.Compared with P. armeniaca group， the t1/2 of amygdalin in the plasma of rats in E. sinica-P. armeniaca drug-pair group was significantly shortened， and CLZ/F was significantly increased （P＜0.01）； the tmax of bitter amygdalin in the cerebrospinal fluid was significantly shortened， and the AUC0-10.67 h， CLZ/F， and VZ/F were significantly increased （P＜0.01）. CONCLUSIONS The combination of E. sinica and P. armeniaca accelerates the absorption and elimination of ephedra alkaloids， thus reducing the accumulation of ephedra alkaloids in the bronchial asthma model rats.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

Objective To investigate the protective effects and underlying mechanisms of sodium butyrate on rats exposed to hypoxia and cold conditions.Methods Fifty-eight male SD rats (aged 7～8 weeks,weighing 240～260 g ) were randomly divided into normoxia normothermia saline control (NNC ) group (n=10),normoxia normothermia sodium butyrate(NNB)group(n=10),hypoxia cold saline control (HCC) group (n=19),and hypoxia cold sodium butyrate (HCB)group (n=19).The intragastric dose of sodium butyrate was 200 mg/kg for the NNB and HCB groups,while the NNC and HCC groups were given normal saline of 5 mL/kg.①After continuous intragastric administration for 7 d,the rats in the HCC and HCB groups were placed in a low-pressure hypoxic chamber to simulate an altitude of 5000 m and exposed to a temperature of 8 ℃ for 7 d.Subsequently,blood samples were collected from the abdominal aorta for blood gas analysis,blood routine test,and detection for serum biochemical indicators.ELISA was used to determine serum inflammatory cytokines and endocrine hormones.The rats in the NNC and NNB groups(n=10)were fed outside the chamber and underwent the same tests in 7 d later to evaluate the protective effects of sodium butyrate on the body.②Core body temperature monitoring was conducted to assess the impact of sodium butyrate on the rmoregulation in rats exposed to hypoxia and cold(n=3).③Hypoxia exercise tolerance of the HCC group and HCB group in a hypoxic chamber (11％O2 )was evaluated for their hypoxia resistance (n=6).Results Compared to the NNC group,the rats in the HCC group exhibited significant decreases in arterial oxygen saturation (SaO2 )and arterial oxygen partial pressure (PaO2 ),serum levels of IL-4,estradiol (E2)and cortisol (F),core temperature,and exercise duration (P<0.05),and had notably increased levels of red blood cell (RBC)count,hemoglobin (HGB),hematocrit (HCT),cardiac troponin (CRDAC-T),uric acid (UA),alanine aminotransferase (ALT),total cholesterol (TC),low-density lipoprotein (LDL),IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF)(P<0.05).Compared to the HCC group,the rats in the HCB group exhibited significant increases in SaO2,PaO2,IL-4,E2,F,corticotropin releasing hormone (CRH)and adrenocorticotropic hormone (ACTH)(P<0.05),remarkably longer exercise duration under hypoxic exposure (P<0.05 ),but decreases in RBC count,serum levels of HGB,HCT,CRDAC-T,UA,ALT,TC,LDL,IL-6,GM-CSF and free thyroxine (FT4 ),and core temperature (P<0.05).Conclusion Sodium butyrate exhibits protective effects on rats exposed to hypoxia and cold conditions,and it is helpful in their adaptation to these hypoxia and cold environments.

Objective To investigate the effect of parent-child alienation on depression in surface ship officers and soldiers based on the theory of"diathesis-stress",and the mediating role of resilience between parent-child alienation and depression in them.Methods A cross-sectional study was conducted on 599 officers and soldiers from a surface ship unit.The participants were surveyed with inventory of alienation toward parents,connor-davidson resilience scale and patient health questionnaire-9 to obtain and analyze their demographic-military characteristics of their depression scores.The participants with depression scores ≥5 were recruited as the subjects,and Spearman correlation analysis was used to explore the correlation among parent-child alienation,resilience and depression.On the basis of hierarchical regression analysis,AMOS software was used to establish a structural equation modelling of intermediary effects.Results The depression score was 1(0,4)in the participants,and the depression scores of those with service length ≥11 years were comparatively higher than those with shorter length.Our results indicated that parent-child alienation was positive correlated with depression(r=0.451,P＜0.001),while resilience was negatively correlated with depression and parent-child alienation(r=-0.412,-0.407,P＜0.001).Regression analysis revealed that parent-child alienation had a direct positive predictive value for depression(β=0.574,P＜0.001),and resilience showed a negative predictive value for depression(β=-0.211,P＜0.01).Model analysis displayed that resilience had a significant mediating role in the effect of parent-child alienation on depression among these surface ship officers and soldiers,with an effect value of 0.088,and accounting for 15.86％of the total effect.Conclusion Parent-child alienation has a significant influence on depression among surface ship officers and soldiers,with resilience playing a partial mediating role.

Objective To compare the clinical safety and efficacy of CT-guided hook-wire localization of≤10mm pulmonary ground-glass nodule(GGN)via different path ways before video-assisted thoracoscopic surgery(VATS).Methods The clinical data of a total of 128 patients with 10 mm pulmonary GGN,who received CT-guided hook wire localization before VATS at The Third Hospital of Mianyang of China between July 2018 and March 2023,were retrospectively analyzed.According to the puncturing localization path way mode,the patients were divided into vertical puncturing group(n=88)and non-vertical puncturing group(n=40).The number of puncturing times,the time spent for puncturing localization,the success rate of puncture,the operation time of VATS,and puncture-related complications of the two groups were recorded.Results No statistically significant differences in the gender,age,smoking history,GGN location,puncture position,nodule size,density characteristics of GGN,emphysema,and nodules-pleura distance existed between the two groups(all P＞0.05).Compared with non-vertical puncturing group,in vertical puncturing group the number of puncturing times was smaller,the time spent for localization was shorter,the incidence of pneumothorax was lower,and the operation time of VATS was shorter,the differences in all the above indexes between the two groups were statistically significant(all P＜0.05);and the subgroup analysis of patients whose GGN was overlapped with rib shadow obtained the same results.Binary logistic regression analysis revealed that non-vertical puncturing and the number of puncturing times were the independent risk factors for the occurrence of pneumothorax.Conclusion CT-guided hook-wire localization of≤10mm pulmonary GGN before VATS is clinically safe and effective.Under the condition when the lesion can be localized within the range of 2.0cm and the shadow overlapping of GGN with the rib and blood vessel can be effectively avoided,vertical puncturing path way mode should be preferred,which can effectively reduce the incidence of pneumothorax and shorten the operation time of VATS.

Purpose To investigate the clinical value of multi-center digital mammography radiomics nomogram model in predicting triple-negative breast cancer(TNBC).Materials and Methods The digital mammograms of 462 patients with pathologically confirmed breast cancer from November 2016 to March 2022 were retrospectively analyzed,including 243 cases from Yijishan Hospital of Wannan Medical College(institution 1),106 cases from Fuyang People's Hospital(institution 2)and 113 cases from Taihe People's Hospital(institution 3).According to the results of immunohistochemistry,a total of 349 breast cancer patients in institution 1 and institution 2 were randomly divided into the training group(244 cases,including 41 TNBC and 203 non-TNBC)and the validation group(105 cases,including 18 TNBC and 87 non-TNBC)according to the ratio of 7∶3,113 breast cancer patients(24 TNBC and 89 non-TNBC)from institution 3 were included in the external validation group.Comparing the mediolateral oblique and cranial cauda digital mammography images,the mammography imaging with larger lesion areas were selected,and the image segmentation and radiomics feature extraction were performed.The radiomics model was constructed by using Logistic regression.The clinicopathological parameters and radiomics scores were used to construct a nomogram.Receiver operating characteristic and decision curve analysis were used to evaluate the model performance.To compare The predictive performance between the models was compared.Results Finally,four radiomics features closely related to TNBC were selected to construct an radiomics model.The area under the curve,sensitivity and specificity of TNBC predicted by the radiomics model in training group,validation group and external test group were 0.868,90.24%and 72.91%,0.827,72.22%and 75.86%,0.837,70.83%and 78.65%,respectively.The area under the curve,sensitivity and specificity of TNBC predicted by the combined model in the training group,validation group and external test group were 0.903,80.49%and 86.70%,0.890,77.78%and 88.51%,0.870,62.50%and 85.39%,respectively.The combined model was better than the single image omics model in predicting TNBC,and the difference was statistically significant between the training group and the verification group(Z=2.061,2.064,both P<0.05),but not between the external test group(Z=1.223,P=0.221).In three group,decision curve analysis showed that the nomogram predicted a higher net benefit than the radiomics model for triple-negative breast cancer.Conclusion The radiomics model has high diagnostic efficiency in predicting TNBC,and the nomogram model combined with the radiomics score and histological grading can further improve the prediction efficiency.

Objective To investigate the status of application of the central venous access in the departments of hematology to develop targeted administrative strategies and provide evidence for management.Methods A self-de-signed questionnaire was applied and convenience sampling was adopted in 93 hematology departments from 48 hospitals in 19 provinces(autonomous regions,municipalities).Results A total of 91 valid questionnaires were col-lected,with a valid questionnaire response rate of 97.85％.Among the 91 hematology departments,91(100％),73(80.22％),and 68(74.73％)carried out PICC,central venous catheter,and totally implantable access port catheteriza-tion,respectively.In the evaluation of blood test indicators before central venous access,the items with a higher e-valuation proportion were platelet count(100％)and D-dimer concentration(87.91％),while the evaluation proportion of other items was＜85％.When PICC catheterization,97.80％of hematology departments prefer basilic vein;83.52％of hematology departments used zone insertion method;95.60％of hematology departments had a skin disinfection range of ≥20 cm;98.90％of hematology departments had catheterization under ultrasound guidance;67.03％and 96.70％of hematology departments used the intracardiac electrocardiogram method or ultrasound assisted localiza-tion,postoperative X-ray localization;12.09％and 53.85％of hematology departments carried out tunnel catheteriza-tion and blunt separation expansion techniques,respectively.In terms of maintenance of central venous access de-vices,82.42％of hematology departments used disposable specialized maintenance kits;61.54％of hematology de-partments used transparent patches to fix PICC;45.21％of hematology departments used suture to fix central venous catheters;24.18％of hematology departments used cotton swabs to disinfect infusion joints;60.44％of hematology departments did not use disposable infusion joint disinfection cap;74.73％of hematology departments used gauze compression to prevent puncture site bleeding;only 6.59％hematology departments used antibacterial dressings con-taining chlorhexidine to prevent puncture site infections.In terms of quality management of central venous access devices,94.51％and 86.81％of hematology departments regularly conducted quality inspections of central venous access,and collected,calculated and analyzed relevant data.50.55％of hematology departments conducted complica-tion risk assessments,and 10.99％of hematology departments had established information management systems for venous therapy.Conclusion The implementation rate of PICC catheterization in the hematology department was relatively high,and the insertion operation basically meets the standard requirements.The evaluation before central venous access catheterization was relatively completed,and the maintenance and management are relatively stan-dardized.However,the evaluation of blood test indicators before the placement of central venous access urgently needs to be standardized and unified.When PICC catheterization,attention should be paid to the application of new technologies,and the information management of venous therapy needs to be improved.

Objective:To explore the characteristic pathological manifestations of non-HLA antibodies after kidney transplantation (KT) and examine the differences of MFT values of non-HLA antibodies in different pathological manifestations.Methods:The study was conducted on KT recipients at the First Affiliated Hospital of Zhengzhou University from February 2021 to June 2023 with unexplained elevated serum creatinine. Patients undergoing pathological puncture and concurrent HLA antibody testing were included, focusing on those with DSA (MFI>4 000) and non-HLA antibody negativity. According to the detection results of non-HLA and HLA antibodies, they were assigned into two groups of non-HLA antibody positive (45 cases) and HLA-DSA positive (28 cases). Both non-HLA and HLA antibodies were detected by luminex single antigen microbeads, χ2, t or Mann-Whitney U nonparametric tests were utilized for examining the inter-group differences in pathological manifestations. The recipients with positive non-HLA antibodies were grouped according to the differential pathological features[microvascular inflammation group (22 cases) and non-microvascular inflammation group (23 cases), interstitial fibrosis group (39 cases) and non-interstitial fibrosis (9 cases) ]. MFI values of non-HLA antibodies were standardized and heat map was generated with R language ComplexHeatmap package. The differences of response values of non-HLA antibodies with different pathological manifestations were examined by rank-sum test. Results:The positive rates of microvascular inflammation were 48.9% (22/45) and 82.1% (23/28) in HLA-DSA positive and non-HLA antibody positive groups with statistical significance ( χ2=8.073, P=0.006). The positive rates of interstitial fibrosis in two groups were 80.8% (36/45) and 53.6% (15/28) and the difference was statistically significant ( χ2=5.726, P=0.021). The relative levels of anti-arachnotoxin receptor 1 (Latrophilin 1, LPHN1), keratin 8 (KRT8), keratin 18 (KRT18) and Sjogren's syndrome antigen B (SSB) were higher in microvascular inflammation group than those in non-microvascular inflammation group. The differences were statistically significant [559.50 (262.00, 801.25) vs 285.00 (183.00, 460.00), P=0.024; 504.50 (369.5, 725.25) vs 317.00 (231.50, 458.00), P=0.014; 672.50 (454.50, 969.50) vs 399.00 (246.50, 772.50), P=0.030; 967.50 (482.00, 2 066.50) vs 399.00 (246.50, 772.50), P=0.033]. The relative levels of anti-cyclic citrullinate peptide (CCP), colony-stimulating factor 2 (CSF2), intercellular adhesion molecule 1 (ICAM1) and collagen Ⅳ antibody were higher in interstitial fibrosis group than those in non-interstitial fibrosis group with statistical significance [100.00 (79.88, 167.50) vs 64.50 (37.00, 89.00), P=0.016; 146.25 (93.38, 244.75) vs 87.00 (66.00, 105.00), P=0.041; 132.50 (106.38, 229.50) vs 95.00 (55.00, 125.00), P=0.037; 432.50 (280.75, 653.75) vs 208.00 (192.00, 301.00), P=0.028]. Conclusions:As compared with HLA-DSA, the characteristic pathological manifestations of non-HLA antibodies post-KT include a lower incidence of microvascular inflammation and a higher incidence of interstitial fibrosis. For non-HLA antibody response values of characteristic pathological manifestations, the expressions of different non-HLA antibodies vary statistically.

Objective: To evaluate the effectiveness of varicella vaccine in varicella outbreaks and to analyze the influencing factors, and to provide a reference for making the targeted prevention and controlling measures. Methods: A total of 3 888 students with no history of varicella were selected from 2 schools with varicella outbreak in Guangdong Province in 2021, a retrospective cohort study was conducted by using questionnaire survey, rate ratio ( RR ) and vaccine effectiveness ( VE ) values were calculated and Logistic regression was uses to analyze the factors influencing the protective effect of varicella. Results: There were 138 confirmed cases of varicella among the participants. There was no significant sex difference in the vaccination rate( χ 2=1.36, P =0.51), but there was significant difference in the vaccinattion rate of different age groups( χ 2=555.82, P <0.01). The overall protective effect of VarV was 66.94%(95% CI =56.17%-77.71%), and the protective effect of 2 doses of vaccine( VE = 90.02% , 95% CI =83.13%-96.90%) was higher than that of 1 dose( VE =49.40%, 95% CI =32.36%-66.44%)( χ 2=24.93, P < 0.01 ). The high fever rates in the vaccinated and unvaccinated groups were 7.69% and 25.81%, with significant difference( χ 2= 6.29 , P <0.05). The rates of moderate and severe skin lesions of vaccinated and unvaccinated groups was 20.00% and 50.00%, respectively, and the difference was statistically significant( χ 2=11.32, P <0.01). The protective effects of varicella vaccine against high fever and moderate to severe rash were 70.19%(95% CI =42.11%-98.27%) and 60.00%(95% CI =38.15%-81.85%). Stratified analysis showed that there were significant differences in different years of vaccination( χ 2=37.87, P <0.05), while there were no significant differences in age of vaccination and vaccine manufacturer ( P >0.05). Conclusion Varicella vaccination can prevent chickenpox infection and reduce the severity of the disease. However, the efficacy of varicella vaccine was affected by vaccination years. It is recommended to improve the vaccination coverage of varicella vaccine to prevent the outbreak of the epidemic.

Objective: To investigate the level of chronic disease prevention and control literacy and its influencing factors among residents in Taizhou City, Zhejiang Province, so as to provide insights into formulating health education strategies on chronic diseases. Methods: A total of 32 313 permanent residents at ages of 15 to 69 years were sampled in Taizhou City using the multi-stage stratified random sampling method and probability proportionate to size sampling method (PPS). Subjects' demographic characteristics and chronic disease prevention and control literacy were collected using the national health literacy surveillance questionnaire. The levels of chronic disease prevention and control literacy from 2017 to 2022 were evaluated and standardized by the population data provided by Taizhou Municipal Bureau of Statistics. Factors affecting the chronic disease prevention and control literacy were identified using a multivariable logistic regression model. Results: Totally 32 313 questionnaires were distributed, and 32 258 valid questionnaires were recovered, with an effective recovery rate of 99.83%. The median age of participants was 51.00 (interquartile range, 19.00) years. There were 15 754 men (48.84%) and 16 504 women (51.16%), and 11 060 urban residents (34.29%) and 21 198 rural residents (65.71%). Farmer was the predominant occupation (16 003 residents, 49.61%). The level of chronic disease prevention and control literacy among residents in Taizhou City was 32.97%, which was 22.58%, 26.41%, 33.48%, 34.44%, 38.53% and 39.68% from 2017 to 2022, respectively, showing an upward trend (P<0.05) with a cumulative growth rate of 17.10%. Multivariable logistic regression analysis showed that age (15 to 24 years, OR=1.566, 95%CI: 1.309-1.874; 25 to 34 years, OR=1.345, 95%CI: 1.173-1.542; 35 to 44 years, OR=1.482, 95%CI: 1.311-1.675; 45 to 54 years, OR=1.203, 95%CI: 1.078-1.343), educational level (primary school, OR=1.728, 95%CI: 1.546-1.932; junior high school, OR=2.211, 95%CI: 1.977-2.472; high school/vocational high school/technical secondary school, OR=3.368, 95%CI: 2.972-3.817; college or above, OR=7.271, 95%CI: 6.313-8.373), occupation (farmer, OR=0.739, 95%CI: 0.663-0.825; others, OR=0.778, 95%CI: 0.694-0.872), place of residence (urban areas, OR=0.903, 95%CI: 0.852-0.956) and annual household income (30 000 to 49 999 Yuan, OR=1.138, 95%CI: 1.030-1.259; 50 000 to 99 999 Yuan, OR=1.239, 95%CI: 1.143-1.342; 100 000 to 199 999 Yuan, OR=1.445, 95%CI: 1.334-1.566; 200 000 Yuan and above, OR=1.803, 95%CI: 1.629-1.997) were influencing factors for chronic disease prevention and control literacy. Conclusions The level of chronic disease prevention and control literacy among residents in Taizhou City shows an upward trend from 2017 to 2022, with age, educational level, occupation, place of residence and annual household income as the influencing factors.