OBJECTIVE To evaluate the cost-effectiveness of tislelizumab monotherapy in the second-line treatment of advanced or metastatic esophageal squamous cell carcinoma （ESCC），so as to provide reference for rational use of drug in clinic. METHODS A three-state partitioned survival model was constructed from the perspective of China’s health system， based on the data of RATIONALE-302 study，with simulation time limit of 10 years， cycle period of 1 month. The incremental cost-effectiveness ratio （ICER） was calculated with quality-adjusted life year （QALY） as utility index. The cost-effectiveness of tislelizumab monotherapy was compared with that of chemotherapy for second-line treatment of advanced or metastatic ESCC by cost-utility analysis. The stability of basic analysis results was validated through sensitivity analysis and scenario analysis. RESULTS The results of basic analysis showed that compared with chemotherapy group， incremental cost per capita of tislelizumab group was 35 025.32 yuan，and incremental utility per capita was 2.71 QALYs； ICER was 12 892.31 yuan/QALY， which was far lower than the willingness-to-pay （WTP） threshold of 3 times of China’s per capita gross domestic product （GDP） 242 928 yuan in 2021. The results of univariate sensitivity analysis showed that parameters such as the cost of apatinib， the utility value of disease progression status and the cost of adverse reactions in the chemotherapy group had a great impact on the ICER value， but these parameters could not cause the reversal of the basic analysis results. Probabilistic sensitivity analysis showed that WTP threshold was higher than 80 000 yuan/QALY，the probability of tislelizumab monotherapy possessed cost-effectiveness was 100%. Results of scenario analysis showed that in which model simulation time lasted for 5 or 20 years，ICER of tislelizumab was 8 331.00 yuan/QALY and 12 981.00 yuan/QALY， which were less than 3 times of China’s per capita GDP in 2021 as WTP threshold. CONCLUSIONS When three times of China’s GDP per capita in 2021 is taken as the WTP threshold， the second-line treatment of tirelizumab monotherapy for advanced or metastatic ESCC is more cost-effective than chemotherapy.

Objective:To investigate the effect of biological maternal sounds on blood gas analysis index, mechanical ventilation time, oxygen therapy time and hospital stay in mechanically ventilated children with severe pneumonia.Methods:This study was a randomized controlled trial. From June 2020 to November 2020, 128 mechanically ventilated children with severe pneumonia in Hunan Children′s Hospital were selected by convenient sampling method and divided into four groups with 32 cases in each group by random number table method. Group A was given routine nursing care, group B was given mother sounds, group C was given mother cardiotone, group D was given biological maternal sounds. Data of blood gas analysis index, mechanical ventilation duration, oxygen therapy duration, hospital stays were collected for comparative analysis.Results:Finally, group A, B, C, and D included 28, 30, 28 and 28 cases, respectively. There was no statistically significant difference in PaO 2 among the four groups on the 1st to 2nd day after intervention ( P>0.05), but PaO 2 on the 3rd to 7th day after intervention were (75.57 ± 12.88), (77.71 ± 15.81), (78.21 ± 14.51), (78.64 ± 17.71), (79.04 ± 11.57) mmHg (1 mmHg=0.133 kPa), (81.71 ± 17.89), (82.93 ± 18.36), (82.68 ± 15.47), (83.25 ± 14.24), (83.77 ± 13.90) mmHg, (80.89 ± 18.78) (82.11 ± 13.34), (82.96 ± 14.20), (83.43 ± 14.37), (83.68 ± 12.64) mmHg, (84.54 ± 18.77), (86.29 ± 10.94), (86.96 ± 10.53), (87.46 ± 12.64), (89.08 ± 12.21) mmHg, with statistically significant differences ( F values were 41.17 - 332.68, all P<0.01). Further pairwise comparison revealed that PaO 2 in group B and group C were higher than those in group A on the 3rd to 7th day after intervention, while those in group D were higher on the 3rd to 7th day after intervention than those in group A, B, and C, with statistically significant differences( t values were 3.35- 4.75, all P<0.01). There was no statistically significant difference in PaCO 2 among the four groups on the 1st to 4th day after intervention ( P>0.05), but PaCO 2 on the 5th to 7th day after intervention was (47.31 ± 2.89), (46.18 ± 2.06), (41.94 ± 2.09) mmHg, (44.73 ± 1.76), (41.38 ± 1.30), (38.33 ± 1.16) mmHg, (44.81 ± 1.24), (41.23 ± 1.89), (38.73 ± 2.55) mmHg, (40.83 ± 1.78), (37.87 ± 1.43), (34.78 ± 2.05) mmHg, with statistically significant differences ( F=29.48, 36.12, 34.52, all P<0.05). Further pairwise comparison revealed that PaCO 2 in group B and group C were lower than those in group A on the 5th to 7th day after intervention, while PaCO 2 in group D were lower than those in groups A, B, and C, with statistically significant differences ( t values were 3.37-4.85, all P<0.01). During the analysis of PaO 2 and PaCO 2 in the four groups at different time points, the interaction effects were not statistically significant ( P>0.05). There was no significant difference in invasive mechanical ventilation duration, non-invasive mechanical ventilation duration and hospital stay among the four groups after intervention ( P>0.05). The oxygen therapy time of the four groups were (8.61 ± 6.40), (6.17 ± 4.80), (6.23 ± 2.75), and (3.75 ± 2.10) days, with statistically significant differences ( F=17.27, P<0.01). Further pairwise comparison revealed that the oxygen therapy time in group B and group C was shorter than that in group A, while group D was significantly shorter than that in groups A, B, and C, with statistically significant differences ( t values were 4.02-4.74, all P<0.01). Conclusions:Biological maternal sounds is superior to maternal sound and mother cardiotone in improve the blood gas analysis index, shorten the oxygen treatment time, which is worthy of clinical promotion in neonatal unaccompanied ward.

Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs' effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.
Aging ; Animals ; Autoimmune Diseases ; Disease Models, Animal ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism* ; Mice ; Mice, Inbred C57BL ; Th17 Cells/metabolism* ; Uveitis/pathology* ; Virulence

Objective:To deeply understand the real emotional experience and needs of the parents of dying newborns, so as to provide a reference for future neonatal palliative care.Methods:From February to October 2021, purposeful sampling was used to select 15 parents of dying newborns in the Department of Neonatology of Hunan Children's Hospital as the research object. A qualitative research design was conducted, and the semi-structured interview method was used to conduct in-depth interviews with the research subjects, and NVivo 10.0 software was used for data analysis.Results:A total of 3 themes were extracted, namely, the ambivalence when giving up treatment, negative life effects after giving up, needs and expectations.Conclusions:Parents of dying newborns generally have ambivalence when they give up treatment. After giving up, they will show emotions such as sadness and helplessness, self-blame and regret, and depression. Understanding the real emotions and inner needs of the parents of dying newborns helps medical and nursing staff to pay attention to parents' negative psychology and understand their needs, and provide parents with targeted psychological support and other care, so as to help the parents of dying newborns and their families through a special period.

Objective:To analyze the incidence, biochemical and molecular characteristics, and gene mutation spectrum of neonatal methylmalonic acidemia (MMA) in Shaanxi province.Methods:This study involved 146 152 newborns undergoing neonatal screening for methylmalonic acidemia by tandem mass spectrometry in Northwest Women's and Children's Hospital from January 2014 and December 2019. Clinical manifestations and follow-up data of newborns diagnosed with MMA and their acylcarnitine profiles and gene mutations were analyzed. According to whether they had elevated homocysteine or not, these patients were divided into two groups, the complicated group and the isolated MMA group. The control neonates were those excluded from having methylmalonic acid by re-examination. Kruskal-Wallis and Mann-Whitney U test was conducted for statistical analysis. Results:(1) Twenty-one cases of MMA were confirmed with an incidence of 1/6 960, including 11 cases (52.4%) of isolated MMA (isolated MMA group) and 10 (47.6%) complicated by elevated homocysteine (complicated group). Eight patients in the isolated group had symptoms within one month after birth, mainly feeding difficulties, vomiting, drowsiness, poor response and infection, and five died. Patients in the complicated group were all diagnosed before developing typical clinical symptoms, and no developmental abnormalities were reported during follow-up. (2) Blood propionyl carnitine and its ratios to acetylcarnitine and free carnitine in the isolated MMA and complicated groups were higher than those in the control group [ M (min-max), 9.26 (3.70-37.78) μmol/L and 7.27 μmol/L (3.58-13.62 μmol/L) vs 4.51 μmol/L (1.48-8.69 μmol/L), H=23.239; 1.12 (0.32-2.43) and 0.74 (0.36-1.90) vs 0.25 (0.09-0.45), H=47.061; 0.94 (0.12-1.92) and 0.56 (0.18-1.03) vs 0.17 (0.06-0.38), H=36.868; all P<0.001]. The blood methionine level in the complicated group was significantly lower than that in the isolated MMA group [7.64 μmol/L (3.40-19.25 μmol/L) vs 24.22 μmol/L (10.73-56.55 μmol/L), U=3.000, P<0.001]. (3) All 21 patients carried complex heterozygous mutations or homozygous mutations in pathogenic genes, including 15 distinct MMUT mutations and 13 distinct MMACHC mutations. In the isolated MMA group, the most common mutation was c.323G>A (p.Arg108His) in the MMUT gene with a positive rate of 13.6%, and an unreported mutation, c.1676+11A>G, with unidentified clinical significance, was also found. The most common mutations in the complicated group were c.609G>A (p.Trp203Ter) and c.567dupT (p.Ile190fs) in the MMACHC gene, and the positive rates were both 20.0%. Moreover, two unreported variants, c.430-2A>C and c.648_650delAGA (p.216_217delSEinsS), were detected and suspected to be pathogenic. Conclusions:MMA is not uncommon in Shaanxi province. Children with isolated MMA tend to be more severe clinically. The identification of hotspot mutations, including c.609G>A (p.Trp203Ter) and c.567dupT (p.Ile190fs) in MMACHC gene and c.323G>A (p.Arg108His) in MMUT gene, provides a foundation for further genetic screening, counseling, and prenatal diagnosis, and is conducive to reduce the mortality and disability rate of neonatal MMA.

Objective To analyze the effects of losartan and amlodipine on leptin,adiponectin and insulin sensitivity in obese hypertensive patients.Methods 126 patients with obesity related hypertension were selected,and they were randomly divided into losartan group and amlodipine group according to the digital table,63 cases in each group.The losartan group were treated with losartan 50mg/time,1 time/d.The amlodipine group was given amlodipine 50mg/time,1 time/d.The two groups were given the corresponding drugs for 16 weeks.The body mass index (BMI),heart rate,systolic blood pressure (SBP),diastolic blood pressure (DBP),leptin,adiponectin,HOMA-IR and norepinephrine(NE) levels were measured before and after treatment in the two groups.Results After treatment,the BMI of the losartan group decreased significantly,the difference was statistically significant (t =6.660,P ＜ 0.05),but there was no significant difference in heart rate (t =0.180,P ＞0.05).After treatment,the BMI of the amlodipine group decreased significantly (t =3.647,P ＜ 0.05),heart rate increased significantly,the difference was statistically significant (t =3.098,P ＜ 0.05).After treatment,the BMI and heart rate in the losartan group were significantly lower than those in the amlodipine group,and the differences between the two groups were statistically significant (t =3.106,3.256,all P ＜0.05).After treatment,the SBP and DBP in the two groups were significantly decreased,the differences were statistically significant (tlosartan group =9.503,13.095;tamlodipine group =10.254,11.776,all P ＜ 0.05),there were no statistically significant differences between the two groups (t =0.975,0.659,all P ＞ 0.05).After treatment,the level of adiponectin in the losartan group was significantly increased,the leptin level and HOMA-IR score decreased significantly,the differences were statistically significant (t =4.462,2.004,5.572,all P ＜ 0.05),there was no significant difference in the level of NE (t =0.481,P ＞ 0.05).After treatment,NE level of the amlodipine group was significantly higher,the difference was statistically significant (t =6.090,P ＜ 0.05),there were no statistically significant differences in the levels of leptin,adiponectin and HOMA-IR score (t =0.126,0.053,0.448,all P ＞ 0.05).Conclusion Losartan and amlodipine can effectively control hypertension,but losartan can effectively regulate the metabolic disorder of obesity related hypertension patients with obesity alone,therefore,losartan alone has more significant effect compared with amlodipine.

Objective To assess clinical strategy of family-centered care in neonatal extension nursing. Methods We chose 260 cases in Neonatology Department of Hunan Children′s Hospital from February to August on 2014 and randomized them into two groups, observation group and control group. Families received routine education in two groups. However, we educated the families how to feed, keep warmth, bath, disinfect umbilical region and caring button and their question by telephone after 3, 7days discharged from our center in the observation group. We compared weight, height, increasing of head circumference, and families satisfaction between two groups. Results In the observation group, the neonate weight was (4 776. 88 ± 446. 59)g, height (54. 76 ± 1. 28) cm, head circumference (37. 16 ± 0. 71) cm, which all were better than those of the control group (t =2. 712,6. 518, 9. 455;P <0. 05). The families′ satisfaction of observation group (99. 2%) compared 85. 8% in the control group (χ2 = 16. 86,P < 0. 05). Conclusions Family-centered nursing education can meet the needs of the patients and their families, which can help to improve the development of neonatal growth and the satisfaction of families.

OBJECTIVE:To observe the clinical efficacy and safety of Kudiezi injection combined with alprostadil in the treat-ment of posterior circulation ischemic vertigo. METHODS:Totally 180 patients with posterior circulation ischemia were randomly divided into group A,group B and group C. All patients were given aspirin,atorvastatin,nutrition nerve,antihypertensive,hypo-glycemic and other conventional treatment. On this basis,group A was given Alprostadil injection 10 μg,adding into 0.9% Sodium chloride injection 100 ml,iv,once a day;Kudiezi injection 30 ml,adding into 0.9% Sodium chloride injection 250 ml,iv,once a day. Group B was given Alprostadil injection(the same usage as group A);group C was given Kudiezi injection(the same usage as group A). The course was 14 d. The clinic data was observed,including clinical efficacy;blood flow velocity in left vertebral ar-tery(LVA),blood flow velocity in right vertebral artery(RVA),blood flow velocity of basilar artery(BA),changes of peak laten-cy(PL)and incubation period latency(IPL)before and after treatment;and the incidence of adverse reactions. RESULTS:The to-tal effective rate in group A was significantly higher than group B and C,with significant difference(P<0.05). After treatment,the blood flow velocity of LVA,RVA and BA in each group were significantly higher than before,group A was higher than group B and C;PL-Ⅰ,PL-Ⅲ,PL-Ⅴ,IPL-Ⅰ-Ⅲ and IPL-Ⅲ-Ⅴ were significantly lower than before,group A was lower than group B and C,with significant differences(P<0.05);however,there were no significant difference between group B and C(P>0.05). There were no obvious adverse reactions during treatment. CONCLUSIONS:Kudiezi injection combined with alprostadil has better effica-cy than only Kudiezi injection or alprostadil in the treatment of posterior circulation ischemic vertigo,with good safety.

Calcium Ionophores ; metabolism ; Female ; Fertilization in Vitro ; adverse effects ; Humans ; Infant, Newborn ; Karyotype ; Male ; Oocytes ; cytology ; metabolism ; Sperm Injections, Intracytoplasmic ; adverse effects

Objective To investigate the clinicopathologic characteristics of premalignant and malignant endometrial polyps (EP) in premenopausal and postmenopausal women.Methods A retrospective analysis was conducted in 42 cases of premalignant and malignant EP from 1993 to 2012.Polyps were classified into premenopausal (group A,10 cases) and menopausal (group B,32 cases),including 26 cases of endometrioid adenocarcinoma,4 of clear cell carcinoma,9 of serous adenocarcinoma,and 3 of atypical hyperplasia.Results The prevalence rate of premalignant and malignant EP was 1.42％ (42/2 965),the prevalence rate of malignancy in postmenopausal and postmenopausal women was 0.48％ (10/2 064) and 3.55％ (32/901),respectively.The mean size of EP was (1.6 ± 0.8) cm,abnormal uterine bleeding was positive in 90％ (38/42) of cases.The EP pathological diagnosis showed all were endometrioid adenocarcinoma in group A,while there were 4 of clear cell carcinoma,9 of serous adenocarcinoma in group B.The mean size of EP was (1.1 ± 0.6) and (1.7 ± 0.9) cm in group A and B respectively (P ＜0.05).According to immunohistochemistry,all cases of group A were ER positive,but 41％ (11/27) of group B were ER negative (P =0.059).The PR positive rate was 8/9 and 56％ (15/27) in group A and B,respectively (P =0.169).Conclusions The risk of the EP malignancy rate is higher,while ER,PR positive rate are lower in postmenopausal womcn.Postmenopausal EP,especially accompanied by abnormal uterine bleeding and large polyps should be removed as soon as possible.