Objective To establish a quality control method for monitoring the blood concentrations of cyclosporin A and tacrolimus by HPLC-MS/MS,and to evaluate the quality control samples using the Westgard multi-rule theory.Methods HPLC-MS/MS was used to determine the concentration of cyclosporin A and tacrolimus in human whole blood.The quality control samples of low,medium and high concentration levels in the therapeutic drug monitoring process were statistically analyzed,Levery-Jennings and Z-score quality control charts were drawn,and the Westgard multi-rule theory was applied for in-house quality control evaluation.Results The established method was fully validated with linear ranges of 10.40-1 040.00 ng·mL-1 and 0.50-49.50 ng·mL-1,the quantification limits were 10.40 and 0.50 ng·mL-1,respectively.The extraction recoveries were 108.61％-113.24％and 101.99％-109.37％,respectively.The matrix factors normalized by internal standard were 106.68％-111.27％and 95.70％-97.81％for cyclosporin A and tacrolimus,respectively.The intra-day and inter-day accuracy and precision were less than 15.0％.Other parameters were also validated and met the acceptance criteria.Levery-Jennings and Z-score quality control charts showed that there were 4 warnings(violation of the 12s rule)in the results of the 26 groups of quality control samples in the third quarter of 2022,and no phenomenon was observed to be out of control.Conclusion The established in-house quality control system for therapeutic drug monitoring of cyclosporin A and tacrolimus can effectively ensure the accuracy of blood drug concentration detection.

Objective:To explore the correlation between post-traumatic stress disorder(PTSD),resilience and quality of life of front-line medical staff in public health emergencies.Methods:From Nov to Dec 2020,the medical staff of 4 COVID-19 designated hospitals in Wuhan were investigated with the general demographic questionnaire,10-item Connor-Davidson Resilience Scale,PTSD Checklist for DSM-5 and Simplify Qualify of Life Scale.Spearman correlation analysis and hierarchical regression analysis were used to investigate the correlation between PTSD,resilience and quality of life.Results:A total of 545 questionnaires were collected in this survey and the valid effective rate was 97.8% (533/545).The score of psychological resilience,PTSD and quality of life of medical staff were 26(20,30),17(8,25),and 20(18,23),respectively.And 13.1% (70/533)of medical staff had obvious PTSD symptoms.There were significant differences in the score of quality of life among medical staff with different genders,occupations and PTSD levels.Spearman correlation analysis results showed that the score of PTSD was negatively correlated with quality of life and psychological resilience(r=-0.488 and-0.464,P＜0.01).The score of psychological resilience was positively correlated with the score of quality of life(r =0.578,P＜0.01).Psychological resilience and PTSD were important predictors of quality of life,with an explanatory capacity of 37.0% .Conclusions:PTSD is a risk factor for quality of life,and psychological resilience is a protective factor for quality of life.In public health emergencies,improving psychological resilience,preventing and treating PTSD can improve the quality of life of medical staff.

Objective To investigate the protective effect of herba artemisiae scopariae extract on multidrug resistance protein 3(MDR3)gene mutation-induced neonatal parenteral nutrition-associated cholestasis(PNAC)and its possible mechanism.Methods ①Human primary hepatocytes were treated with cell culture in vitro,CRISPR/Cas9 lentivirus infection and MDR3 mutant gene lead-in.The levels of hepatic and biliary biochemical indexes[alanine transaminase(ALT),aspartate transaminase(AST),total bilirubin(TBil),direct bilirubin(DBil),indirect bilirubin(IBil),total bile acid(TBA)]in the supernatant of hepatocytes before and after 16,32,48 hours were compared to determine the time required for fatty acid induction of PNAC hepatocyte model with MDR3 gene mutation.② Human primary hepatocytes were divided into blank control group,MDR3 gene wild type group,MDR3 gene mutation group,and herba artemisiae scopariae extract intervention group according to random number table method.The blank control group was treated with culture medium only,the MDR3 gene wild type group was infected with lentivirus and mixed with wild type MDR3 gene and culture medium,the MDR3 gene mutation group was infected with lentivirus and cultured in culture medium with the mutant genes lead-in of LV-MDR3KI(c.485T>A,c.2793insA,c.1031G>A,c.3347G>A)mutation,while the MDR3 mutant gene was lead-in by lentivirus infection and cultured in culture medium,and then pretreated with 100 g/L herba artemisiae scopariae extract in the herba artemisiae scopariae extract intervention group,then the four groups of hepatocytes were induced with 1%fat emulsion,and the treatment time was the time needed to construct the PNAC hepatocytes model with MDR3 gene mutation.The levels of ALT,AST,TBil,DBil,IBil and TBA in the supernatant of hepatocytes were measured by enzyme-linked immunosorbent assay(ELISA).The mRNA expression abundance of adenosine triphosphate binding cassette proteins(ABCB4,ABCB11,ABCC2,ABCC3,ABCC4)encoding MDR3,bile salt export pump(BSEP),multidrug resistance associated protein(MRP)2-4,and tumor necrosis factor-α(TNF-α)genes were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results Compared to the blank control group and MDR3 gene wild type group,there was no significant difference in the levels of ALT,AST,TBil,DBil,IBil,TBA in the supernatant of MDR3 gene mutant group before and 16 hours after induction with 1%fat emulsion,however after treated with 1%fat emulsion for 32 hours and 48 hours,the levels of ALT,AST,TBil,DBil,IBil,TBA in the supernatant of MDR3 mutant hepatocytes were significantly increased(P<0.05),consequently the time required for fatty acid induction of PNAC hepatocyte model was 32 hours.At 32 hours after treatment with fat emulsion,the levels of ALT,AST,TBil,DBil,TBA in the supernatant of hepatocytes in the herba artemisiae scopariae extract intervention group were significantly decreased[ALT(ng/L):148.3±2.3 vs.164.9±7.0,AST(ng/L):2767.4±78.8 vs.3239.4±107.1,TBil(μmol/L):7.6±0.2 vs.13.6±0.3,DBil(μmol/L):1.8±0.1 vs.5.7±0.2,TBA(μmol/L):3.4±0.2 vs.6.7±0.1,all P<0.05].The ABCB4,ABCC2,ABCC3,ABCC4 mRNA expression of MDR3,MRP2,MRP3,MRP4 in the blank control group,MDR3 wild type group,MDR3 gene mutation group and the herba artemisiae scopariae extract intervention group had no significant difference.The expression of TNF gene mRNA was highly expressed in MDR3 gene mutation group(2-??Ct:1.258±0.200 vs.1.001±0.052),and was low expressed in the herba artemisiae scopariae extract intervention group(2-??Ct:0.387±0.247 vs.1.258±0.200),and there was a significant difference between the two groups(both P<0.05).Compared to the MDR3 gene mutation group,the ABCB11 gene encoding BSEP mRNA expression in the herba artemisiae scopariae extract intervention group was significantly increased(2-??Ct:2.955±0.479 vs.1.333±0.529,P<0.05).Conclusion The herba artemisiae scopariae extract has a protective effect on PNAC induced by MDR3 gene mutation,which may be related to antagonizing inflammatory reaction,decreasing the expression of TNF mRNA and improving the expression of ABCB11 gene encoding BSEP.

Objective To evaluate the accuracy,sensitivity,specificity and economy of HLA-B*5801 gene polymorphisms detection in predicting allopurinol-related severe drug eruption before receiving allopurinol treatment using rapid health technology assessment(rHTA),to provide clinicians and policymakers with an efficient and convenient evidence-based basis.Methods PubMed,Cochrane Library,Web of Science,Embase,WanFang Data,CNKI databases and the official website of health technology assessment(HTA)agency were electronically searched to collect HTA reports,systematic reviews/Meta-analyses and pharmacoeconomic literature on the HLA-B*5801 gene polymorphisms detection from inception to December 31,2023.Two reviewers independently screened studies,extracted data,assessed the included studies'quality,and analyzed and summarised the results.Results A total of 16 literature were included,of which 5 systematic reviews/Meta-analyses and 11 pharmacoeconomic studies.The results showed that the HLA-B*5801 gene mutation rate was significantly higher in patients presenting with severe drug eruption than in the allopurinol-tolerant group(P＜0.05).Two studies reported the sensitivity and specificity of the HLA-B*5801 gene polymorphisms assay for predicting severe drug eruption,the sensitivity of 0.78,0.93,and specificity of 0.96,0.89,respectively.The economic study showed that HLA-B*5801 gene polymorphisms detection before allopurinol treatment was cost-effective in Chinese Han,Korean,Thai populations,but not in British,American(Caucasian or Hispanic),Singaporean and Malaysian populations.Conclusion HLA-B*5801 gene polymorphisms detection before allopurinol treatment and guiding drug use according to the screening results in Chinese Han population can reduce the risk of severe drug eruption and treatment costs.

Objective:In order to explore the impact of corona virus disease 2019(COVID-19)on the hospitalization of children with bronchiolitis and to improve clinicians′ understanding of the characteristics of bronchiolitis during the COVID-19 epidemic.Methods:This was a multicenter clinical study, and the data have been collected from 23 children′s medical centers in China.All the clinical data were retrospectively collected from children with bronchiolitis who were hospitalized at each study center from January 1, 2019 to December 31, 2021.The results included gender, age at hospitalization, length of stay, respiratory syncytial virus(RSV) test results, severity rating, ICU treatment, and the total number of children hospitalized with respiratory tract infection during the same period.The clinical data of children with bronchiolitis in 2019 before COVID-19 epidemic and in 2020、2021 during COVID-19 epidemic were statistically analyzed and compared.Results:According to a summary of data provided by 23 children′s medical centers, there were 4 909 cases of bronchiolitis in 2019, 2 654 cases in 2020, and 3 500 cases in 2021.Compared with 2019, the number of bronchiolitis cases decreased by 45.94% in 2020 and 28.70% in 2021.In 2019, 2020 and 2021, there were no significant differences in gender ratio, age, and duration of hospitalization.Compared with 2019, the ratio of bronchiolitis to the total number of hospitalizations for respiratory tract infection decreased significantly in 2020 and 2021( χ2=12.762, P<0.05; χ2=84.845, P<0.05).The proportion of moderate to severe bronchiolitis cases in both 2020 and 2021 was lower than that in 2019, and the difference was statistically significant ( χ2=4.054, P<0.05; χ2=8.109, P<0.05).There was no statistically significant difference in the proportion of bronchiolitis cases requiring ICU treatment between 2019, 2020, and 2021 ( χ2=1.914, P>0.05).In 2019, a total of 52.60%(2 582/4 909) of children with bronchiolitis underwent RSV pathogen testing, and among them, there were 708 cases with RSV positive, accounting for 28.00%.In 2020, 54.14%(1 437/2 654) of children with bronchiolitis underwent RSV pathogen testing, and there were 403 cases with RSV positive, accounting for 28.04%.In 2021, 66.80%(2 238/3 500) of children with bronchiolitis underwent RSV pathogen testing, and there were 935 cases with RSV positive, accounting for 41.78%.Compared with 2019 and 2020, the RSV positive rate in 2021 showed a significant increase( χ2=99.673, P<0.05; χ2=71.292, P<0.05). Conclusion:During the COVID-19 epidemic, the implementation of epidemic prevention and control measures reduced the hospitalization rate and severity of bronchiolitis, but did not reduce the positive rate of RSV detection.

Objective:To analyze the diagnostic value of sex hormone combined with carcinoembryonic antigen on lymph node metastasis in breast cancer patients.Methods:52 cases of breast cancer patients who underwent surgical resection were collected and divided into non-metastasis group and metastases group after axillary lymph node ultrasonography. The blood samples was collected from patients and the levels of serum estradiol, testosterone, progesterone and carcinoembryonic antigen were detected; The diagnostic value of the above indexes in patients with lymph node metastasis was analyzed; Logistic risk regression model was used to analyze the independent risk factors for lymph node metastasis after surgical resection.Results:There were significant differences between the non-metastatic group and the metastatic group in the largest tumor diameter and menopause (all P<0.05), but there were no significant differences among other general data (all P>0.05). The serum estradiol level in the non-metastatic group was (153.97±35.55) pg/ml, the progesterone level was (0.33±0.05) ng/ml, and the carcinoembryonic antigen level was (11.44±3.77) ng/ml, while the estradiol level in the metastatic group was (207.19±52.11) pg/ml ( t=4.13, P<0.001), progesterone level (0.38±0.04) ng/ml ( t=4.01, P<0.001), carcinoembryonic antigen level (15.41±3.46) ng/ml ( t=3.94, P<0.001). The above three indicators were significantly increased in patients in the transfer group. The area under the curve of estradiol was 0.83, the area under the curve of progesterone was 0.80, the area under the curve of carcinoembryonic antigen was 0.77, the area under the curve of the combination of the three was 0.85, and the area under the curve of the combination of the three was the largest. Logistic risk regression model showed that estradiol, progesterone, and carcinoembryonic antigen levels were independent risk factors affecting lymph node metastasis in breast cancer patients (all P<0.05) . Conclusion:The sex hormone estradiol, progesterone combined with carcinoembryonic antigen has a high diagnostic value for lymph node metastasis in patients with breast cancer, and can independently predict the occurrence of lymph node metastasis in breast cancer patients.

Objective:To explore the risk factors of deep vein thrombosis (DVT) in hospitalized rehabilitation patients.Method:Clinical data of 1 130 patients, 737 males and 393 females with the mean age of 63.0 (54.0, 73.0) years, admitted in the Department of Rehabilitation Medicine of the Second Hospital of Jiaxing from August 2021 to September 2022 were retrospectively analyzed. Patient underwent vascular color ultrasound examination, DVT was detected in 194 cases (DVT group) and not detected in 936 cases (control group). The general clinical data, venous thromboembolism (VTE) risk stratification and traditional VTE risk factors of patients were documented. The risk factors of DVT formation were analyzed with multivariate logistic regression.Results:Compared with the control group, the DVT group had a higher proportion of patients with older age, longer length of hospital stay, and positive D-dimer (all P<0.001). The proportion of patients with high risk of VTE in the DVT group was 49.5% (96/194), which was higher than that in the control group (27.0% (253/936), P<0.01). The proportion of patients with age≥70 years, previous venous thromboembolism, and history of recent (≤1 month) trauma or surgery in the DVT group was significantly higher than that in the control group (all P<0.001). The proportion of patients with primary diagnoses of quadriplegia, hemiplegia or other motor disorders in the DVT group was significantly higher than that in the control group ( P<0.01). Multivariate logistic regression analysis showed that old age ( OR=1.014, 95% CI: 1.012-1.016), length of hospital stay ( OR=1.001, 95% CI: 1.001-1.002), positive D-dimer ( OR=2.508, 95% CI: 2.368-2.655), high risk of VTE ( OR=1.178, 95% CI: 1.10-1.250), quadriplegia ( OR=2.776, 95% CI: 2.552-3.021), hemiplegia ( OR=3.232, 95% CI: 2.996-3.488), motor disorders ( OR=2.308, 95% CI: 2.110-2.525), paraplegia ( OR=1.878, 95% CI: 1.622-2.175), previous venous thromboembolism ( OR=1.385, 95% CI: 1.314-1.460), history of recent (≤1 month) trauma or surgery ( OR=1.987, 95% CI: 1.886-2.093) (all P<0.001) were independent risk factors for DVT in rehabilitation inpatients. Conclusion:Age, length of hospital stay, primary diagnosis of quadriplegia, hemiplegia, paraplegia or other motor disorders, positive D-dimer, high risk of VTE, previous venous thromboembolism, and history of recent trauma or surgery are independent risk factors for DVT in rehabilitation specialty inpatients.

Hypoxemia is a common complication of pneumonia, asthma, and bronchopulmonary dysplasia in children.Rapid identification of hypoxemia is of great significance for the disposal and management of critical children.Pulse oximetry is recognized by the World Health Organization as the best way to monitor hypoxemia in children, and it can monitor pulse oxygen saturation noninvasively and continuously.Based on the related literature at home and abroad, combined with the clinical needs of pediatrics, the " Expert consensus on clinical application of pulse oximetry in children" is formulated to improve the understanding of pediatricians and nurses on the application in pediatric clinical practice, principle, operation techniques, and limitations of pulse oximetry.

Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.

Objective: Recurrence is the most significant feature of depression and the relationship between iron and recurrent depression is still lack of direct evidence in vivo. Methods: Twenty-one patients with depression and twenty control subjects were included. Gradient-recalled echo, T1 and T2 images were acquired using a 3.0T MRI system. After quantitative susceptibility mapping were reconstructed and standardized, a whole-brain and the regions of interest were respectively analyzed. Results: Significant increases in susceptibility were found in multiple recurrent depression patients, which involved several brain regions (frontal lobes, temporal lobe structures, occipital lobes hippocampal regions, putamen, thalamus, cingulum, and cerebellum). Interestingly, no susceptibility changes after treatment compared to pre-treatment (all p>0.05) and no significant correlation between susceptibility and Hamilton Depression Rating Scale were found. Besides, it was close to significance that those with a higher relapse frequency or a longer mean duration of single episode had a higher susceptibility in the putamen, thalamus, and hippocampus. Further studies showed susceptibility across the putamen (ρ2=0.27, p<0.001), thalamus (ρ2=0.21, p<0.001), and hippocampus (ρ2=0.19, p<0.001) were strongly correlated with total course of disease onset. Conclusion Brain iron deposition is related to the total course of disease onset, but not the severity of depression, which suggest that brain iron deposition may be a sign of brain damage in multiple recurrent depression.