Objective:To explore the relevancy between the uridine diphosphate-glucuronylgly-cosyltransferase 1A1 (UGT1A1) gene mutation and the phenotype of indirect hyperbilirubinemia in children.Methods:Sixteen cases with indirect hyperbilirubinemia who visited the Department of Gastroenterology, Children's Hospital of Nanjing Medical University from July 2013 to November 2019 were retrospectively analyzed and were divided into Gilbert syndrome (GS), Crigler-Najjar syndrome type II (CNS-II), and indirect hyperbilirubinemia groups unexplained by UGT1A1 gene mutations. The differences in gene mutation site information and general clinical data were compared. The association between gene mutation spectrum and bilirubin level was explored by t-test analysis.Results:Ten of the sixteen cases with indirect hyperbilirubinemia had GS, three had CNS-II, and three had indirect hyperbilirubinemia unexplained by UGT1A1 gene mutations. A total of six mutation types were detected, of which c.211G?>?A accounted for 37.5% (6/16), c.1456T?>?G accounted for 62.5% (10/16), and TATA accounted for 37.5% (6/16), respectively. Compared with the GS group, the CNS group had early disease onset incidence, high serum total bilirubin ( t ?=?5.539, P ??0.05) and age of onset ( t ?=?0.3611, P ?>?0.05) between the two groups. There was no significant correlation between the number of UGT1A1 gene mutations and serum bilirubin levels. Children with c.1456T?>?G homozygous mutations had the highest serum bilirubin levels. Conclusion:The common pathogenic variants of the UGT1A1 gene sequence are c.1456T?>?G, c.211G?>?A, and TATA, indicating that these site mutations are related to the occurrence of indirect hyperbilirubinemia and have important guiding significance for the etiological analysis of indirect hyperbilirubinemia in children.

OBJECTIVE To evaluate the cost-effectiveness of denosumab and teriparatide in the treatment of postmenopausal osteoporosis in Chinese women， and provide reference for relevant decision-making. METHODS From the perspective of health system in China， Excel 2003 was used to establish Markov model， and cost-utility analysis was used to evaluate the cost- effectiveness of denosumab or teriparatide combined with Calcium carbonate D3 tablets in the treatment of postmenopausal osteoporosis in Chinese women. Pharmacotherapy effects were obtained with network meta-analysis， and cost and health utility value data were obtained from published literature. The model cycle was 1 year， and the simulation time limit was the patient’s lifetime. Univariate sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the effects of model parameter changes on the robustness of the results. Through scenario analysis， the cost-effectiveness of domestic drug cost used as drug cost of terlipatide group was discussed； the influence of residual effects of teriparatide on the results and the cost-effectiveness of sequential use of desumamab after terlipatide withdrawal were also discussed. RESULTS The effect of denosumab regimen was better than that of terlipatide regimen [13.24 quality-adjusted life years （QALYs） vs. 12.96 QALYs]， with lower cost （51 224.64 yuan vs. 167 102.67 yuan）， denosumab regimen was the absolutely superior regimen. The results of single factor sensitivity analysis showed that the cost and discount rate of Terlipatide injection had greater impact on the results. The results of probability sensitivity analysis showed that when three times of China’s per capita gross domestic product （GDP） in 2021 was used as the threshold of willingness to pay， the probability of cost-effectiveness of denosumab regimen was 93.5%. The results of scenario analysis showed that， whether the drug cost of terlipatide regimen which was replaced by domestic drugs， or the residual effect of terlipatide was considered， or desulmonab was used sequentially after two years of terlipide treatment， denosumab regimen was always the absolute advantage regimen. CONCLUSIONS Denosumab combined with Calcium carbonate D3 tablets is more cost-effective than teriparatide combined with Calcium carbonate D3 tablets in the treatment of postmenopausal osteoporosis in Chinese women.

Objective:This study aims to explore the impact of various clinical factors on the risk of polymyxin B induced DKI in patients.Methods:This is a single-center retrospective case-control study. A total of 139 patients receiving polymyxin B intravenous treatment in our hospital from January 1 to December 31, 2020 were collected. Baseline variables between polymyxin B induced DKI group and non-DKI group were compared using the Chi-square test or Fisher's exact test for categorical variables and the T-test or Wilcoxon rank sum test for continuous variables, as appropriate. Statistical analysis was performed using univariate and multivariate Logistic regression models, Logistic regression models, multivariate Logistic regression models, Kaplan Meier curve, as well as Log-Rank test.Results:Among a total of 139 patients receiving polymyxin B treatment, 49 cases have experienced DKI, 90 cases did not. The incidence of DKI was 35.25%. There was no statistical difference in general information of age, gender, and proportion of standard weight between the two groups. Among the related indexes of polycolistin B administration, the proportion of high daily dose [>25 000 U/(kg·d)] and the total dosage of medication in the DKI group were both significantly higher than that in the non-DKI group ( P< 0.05, respectively). Among the organ function indexes, there were significant differences in initial serum creatinine, blood urea nitrogen, uric acid, urinary occult blood and urinary specific gravity between DKI group and non-DKI group 48 hours before polymyxin B administration ( P< 0.05). Binary Logistic regression analysis suggested that daily dose and initial creatinine before medication were independent risk factors for DKI caused by polymyxin B ( P< 0.05). Kaplan-meier survival analysis showed that with the accumulation of Polymyxin B administration, the higher the daily dose of Polymyxin B was, the faster the DKI occurred (Log-Rank P= 0.0194). Conclusions:Using intravenous polymyxin B is associated with the risk of DKI, among which higher initial blood creatinine values and higher daily doses are independent risk factors for DKI.

Objective:To observe any effect of low-frequency whole body resonant stimulation on the ba-lance and walking ability of hemiplegic stroke survivors.Methods:Sixty-six stroke survivors with hemiplegia were randomly divided into a low-frequency resonance training group, a high-frequency vibration training group and a control group, each of 22. All received routine exercise training at individualized intensities. All three groups underwent five 1-minute cycles of 7Hz, 15Hz or 1Hz stimulation twice a day, five days a week for eight weeks. Before and after the intervention, balance and walking ability were evaluated using the Berg Balance Scale, the timed up and go test and a 10m walking test. Step length, step frequency and step speed were also measured.Results:There were no significant differences among the three groups before the training. Afterward, significant improvement was observed in all of the groups in terms of all of the measurements. The average results of the low-frequency resonance training group were at that point significantly better than the other two groups′ averages, while the high-frequency vibration training group′s results were superior to those of the control group.Conclusion:Resonance training at 7Hz is the most effective in improving the balance and walking ability of stroke survivors with hemiplegia.

Objective:To explore the effect of multidisciplinary team cooperation intervention model on the fear of falling (FOF) of postoperative elderly patients during hospitalization.Methods:From January to December 2021, 100 elderly patients with FOF after surgery in the Surgical Ward of the International Medical Department of Peking Union Medical College Hospital were selected by convenient sampling. The patients were randomly divided into the control group and the observation group according to single and double numbers, with 50 cases each. The control group was given routine nursing, and the observation group was given multidisciplinary team cooperation intervention on the basis of routine nursing. The scores of the Modified Fall Efficacy Scale (MFES) were evaluated on the afternoon of the first day of the patient's getting out of bed (inclusion criteria) and the afternoon of the second day of the activity to compare the FOF of the two groups of elderly patients.Results:Before intervention, there was no statistical difference in MFES scores between the two groups ( P>0.05) . After intervention, the MFES score of the observation group was higher than that of the control group, and the difference was statistically significant ( P<0.01) . In the same Morse fall risk grade of low risk, medium high risk and high risk, the difference of MFES score in the observation group was higher than that in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:Multidisciplinary team cooperation intervention can effectively improve the FOF of elderly patients during hospitalization after surgery and promote postoperative rehabilitation.

OBJECTIVE To evaluate the cost-utility of pembrolizumab combined with chemotherapy versus chemotherapy alone in the first-line treatment of advanced or metastatic esophageal carcinoma. METHODS Cost-utility analysis of pembrolizumab combined with chemotherapy versus chemotherapy alone for advanced or metastatic esophageal carcinoma was conducted by using a three-state partitioned survival model from the perspective of health system in China. The model use d a lifetime simulation time frame with 3 weeks as a cycle. The survival data were extrapolated using KEYNOTE- 590 data；cost data were obtained from the median of 2022 public winning bid on Yaozhi network ，among which the price of pembrolizumab was obtained after discounting by a patient assistance program ；utility data were obtained from the literatures ，and a 5％ discount rate was used for both cost and utility. One-way sensitivity analysis and probabilistic sensitivity analysis were also conducted to examine model robustness. RESULTS Analysis of the base case results showed that compared to chemotherapy alone ，the incremental cost-effectiveness ratio （ICER）of pembrolizumab combined with chemotherapy regimens were 950 528.42 yuan/QALY，107 845.39 yuan/QALY and 315 754.56 yuan/QALY for esophageal squamous cell carcinoma （ESCC），programmed deathligand- 1 combined positive score （PD-L1 CPS）≥10 and intention-to-treat population （ITT），respectively. The results of sensitivity analysis verified the robustness of the basic analysis results. CONCLUSIONS Under our healthcare system ，using a threshold of willingness-to-pay of 1-3 times our GDP per capita in 2021，pembrolizumab combined with chemotherapy regimen isn ’t cost-utility compared with chemotherapy alone in the ESCC and ITT subgroups of patients ，while it is cost-utility in the PD-L 1 CPS≥10 subgroup of patients.

OBJECTIVE To evaluate the cost-effectiveness of denosumab and zoledronic acid in the treatment of postmenopausal osteoporosis ，and to provide reference for relevant decision-making. METHODS From the perspective of Chinese health system ，Excel 2003 software was used to establish Markov model ，and cost-utility analysis was used to evaluate the cost-effectiveness of denosumab or zoledronic acid combined with calcium carbonate D 3 in the treatment of postmenopausal osteoporosis. Pharmacotherapy effects were obtained from the network Meta-analysis ，and cost and health-utility value data were obtained from the published literature or network ，etc. The model cycle was 1 year，and the simulation time limit was the patient ’s lifetime. One-way sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the impact of model parameter changes on the robustness of the results ；and the cost-effectiveness of changing the medication cycle of zoledronic acid were explored through scenario analysis. RESULTS Denosumab regimen was more effective than zoledronic acid regimen （12.77 QALYs vs. 11.98 QALYs），and its cost was also higher than zoledronic acid regimen （51 224.56 yuan vs. 49 221.67 yuan）， and the incremental cost-effectiveness ratio was 2 544.14 yuan/QALY. One-way sensitivity analysis showed that the cost of Zoledronic acid injection and that of Denosumab injection had great impact on the results. The results of probabilistic sensitivity analysis showed that when using 3 times of per capita gross domestic product （GDP）in China in 2021 as the threshold of willingness to pay ，the probability of Denosumab regimen being cost-effective was 85.4％. The results of the scenario analysis showed that the Denosumab regimen was still more cost-effective when the dosing cycle of zoledronic acid was changed. CONCLUSIONS Under the threshold of 1-3 times of Chinese per capita GDP in 2021，denosumab combined with calcium carbonate D 3 is more cost-effective than zoledronic acid combined with calcium carbonate D 3 in the treatment of postmenopausal osteoporosis.

OBJECTIVE To evaluate the cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer from the perspective of the Chinese health care system. METHODS A Markov model was developed by using updated four-year survival data from the PACIFIC trial in May 2021 and relevant literature. The cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer was evaluated by using quality-adjusted life years （QALYs）as health output index with 20-year simulation time frame and a 2-week cycling period. The costs and health output were discounted using discount rate of 5％；one-way sensitivity analysis and probabilistic sensitivity analysis were used to examine the robustness of the model simulation results. RESULTS The results of the base analysis showed that compared with placebo group ，durvalumab resulted in 0.73 QALYs at an incremental cost of 1 076 062.86 yuan and an incremental cost-utility ratio （ICER）of 1 467 546.54 yuan/QALY，which was much higher than 3-fold per capita gross domestic products （GDP）in 2020（217 713 yuan）as willingness-to-pay （WTP）threshold. The results of one-way sensitivity analysis showed that the price of durvalumab and discount rate had a great impact on ICER. Probabilistic sensitivity analysis showed no cost-effective advantage for durvalumab when the WTP threshold was three times of GDP per capita in 2020 （217 713 yuan）. CONCLUSIONS From the perspective of Chinese health care system ，there is no cost-effective advantage to the use of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer when the WTP threshold was three times of GDP per capita in 2020.

OBJECTIVE To evaluate the effectiveness， safety and economy of iron isomaltoside in the treatment of iron deficiency anemia using a rapid health technology assessment （HTA） method， and provide an evidence-based basis for clinical decision-making. METHODS PubMed， Embase， Cochrane Library， CNKI， Wanfang database and foreign HTA official websites were systematically searched， and the search time frame of the databases was from the establishment of the database to May 25th 2022. After data extraction and quality evaluation of the literature according to the inclusion and exclusion criteria， a descriptive analysis of the effectiveness， safety and economy of iron isomaltoside in the treatment of iron deficiency anemia was performed. RESULTS & CONCLUSIONS A total of 1 HTA report， 3 systematic reviews/meta-analysis and 5 economic studies were included. In terms of effectiveness， compared with ferric carboxymaltose， the hemoglobin level of patients using iron isomaltoside increased more， but there was no significant difference in the proportion of responding patients； compared with iron sucrose， it had non- inferiority in increasing and maintaining hemoglobin level， and there was no difference in the quality of life. In terms of safety， the incidence of adverse events of ferric carboxymaltose， iron sucrose and iron isomaltoside were 12.0%， 15.3% and 17.0%， respectively. Iron isomaltoside had a lower incidence of hypophosphatemia， compared with ferric carboxymaltose. There was no statistical difference in the incidence of hypophosphatemia among iron isomaltoside， iron sucrose， iron-dextrin and nanocrystalline iron oxide. The conclusion of the incidence of treatment-emergent adverse event， the incidence of serious adverse events and the withdrawal rate of patients due to adverse events was not clear. In terms of economy， the economy of iron isomaltoside is better than that of iron sucrose， and the economy of iron isomaltoside versus that of ferric carboxymaltose had not been finalized.

Clinical data, nutrition support and 6-year follow-up results of a patient with Tricho-hepato-enteric syndrome (THES) diagnosed in the Children′s Hospital of Nanjing Medical University in December 2013 were analyzed.The patient suffered severe malnutrition, growth retardation, hypophosphatemia, hypoglobulinemia, high nutritional risk status and significant intestinal dysfunction.The genetic testing revealed SKIV2 L gene variation in this case of THES.During the acute exacerbation of diarrhea, enteral nutrition and periodical short-term parenteral nutrition were given as nutrition support.Deep-hydrolyzed formula by oral and low-fat, low-residue, high-quality-protein diet was given during the remission phase.At last, the diarrhea and nutritional status of the patient improved gradually.The growth and development, including neuromotor development of the case also caught up to children with the same age, and he was capable of schooling.It is suggested that rational individualized nutrition support can significantly improve intestinal function and nutritional status of children with THES, which overcome the dangerous period, improve the quality of life and prolong the survival time.