OBJECTIVE To analyze the current status and challenges in importing rare disease drugs in China， providing references for optimizing the import process and improving relevant policies. METHODS Questionnaires and interviews were conducted with stakeholders involved in rare disease drug importation， including government departments， multinational pharmaceutical enterprises， healthcare institutions， and patient organizations. This explored the current situation and challenges encountered by each party. Expert opinions were synthesized to propose improvement suggestions. RESULTS A questionnaire survey of representatives from 25 multinational pharmaceutical companies in the rare disease field revealed that these companies had a strong willingness to import rare disease drugs， with 58.33% of them practicing diverse import models. However， significant challenges hindered this process， including unclear regulations （54.17%）， complex approval procedures （45.83%）， and excessively long approval cycles （41.67%）， negatively impacting their motivation. Meanwhile， interviews with 13 experts from government departments， healthcare institutions， pharmaceutical enterprises， and patient organizations identified deficiencies in policy design， approval processes， sampling inspection costs， and communication efficiency with regulators. Additionally， the drug import model in special medical zones also required improvement. CONCLUSIONS The importation of rare disease drugs in China faces challenges such as incomplete policies， inflexible regulatory mechanisms， and insufficient communication channels. It is recommended to enhance the rare disease definition criteria， optimize import incentive policies， and refine regulatory models， so as to further optimize the import process of rare disease drugs and improve relevant policies.

Objective:To explore the construction of management system of dynamic adjustment for supply catalogue of medical consumables based on diagnosis related groups(DRG),so as to realize the fine supervision and management of rational and compliant use for medical consumables.Methods:The management system of dynamic adjustment for supply catalogue of medical consumables was constructed from 6 dimensions(system establishment,hierarchical management,detailed classification,announcement management,strengthening trial and standardizing contract)through analyzed the existing problems.A total of 149 broad headings of using medical consumables in clinical work of Children's Hospital,Zhejiang University School of Medicine from January 2022 to December 2023 were selected.The changes of the ratio of hygienic material's income in medical income,and the ratio of hygienic material's cost in medically overall cost were compared between before adopted the management system of dynamic adjustment for supply catalogue of medical consumables(2022)and after adopted that(2023).Results:After dynamic adjustment,32 broad headings(21.48%)of 149 broad headings of medical consumables were adjusted according to trial process,and 14 broad headings(9.40%)of medical consumables were optimized in the secondary catalogue,and 85 broad headings(57.05%)of medical consumables reduced their product brand,and the use of 8(5.37%)broad headings of medical consumables were stopped.On the premise that both the person-time of outpatient and emergency,and the person-time of discharge increased,the ratio of the income of hygienic material in medical income decreased from 8.02%of 2022 to 7.29%of 2023,and the ratio of hygienic material cost in overall medical cost decreased from 15.38%of 2022 to 14.17%of 2023,and the accumulated cost of medical consumables was reduced by 7.37 million CNY,accounting for 4.1%of the expenditure of medical consumables.Online procurement rates of medical consumables were respectively 93.05%and 94.34%in 2022 and 2023,which showed an increasing trend year by year.Conclusion:The application of management system of dynamic adjustment for supply catalogue of medical consumables can reduce the ratio of consumables of hospital,and improve the management efficiency of medical consumables,and reduce the procurement cost of medical consumables.

Objective:To explore the binding characteristics of N, N-diethyl-2-(2-(4-(2- 18F-fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-DPA-714) and ( R)- N-sec-butyl- N-methyl-4-(3-( 18F-trifluoromethyl)phenyl)quinazoline-2-carboxamide ( 18F-TFQC) to the single nucleotide polymorphisms of the 18×10 3 translocator protein (TSPO), and to evaluate the imaging efficacy and feasibility of those 2 molecular probes in neuroinflammation rat models. Methods:To test the selectivity of 18F-DPA-714 and 18F-TFQC for TSPO polymorphisms, the wild-type (high-affinity binding, HAB) and mutant (low-affinity binding, LAB) sequences of the human TSPO gene were transfected into 293T cells respectively. A competitive inhibition assay was carried out with N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)-3-isoquinoline carboxamide (PK11195) as an inhibitor to determine the binding affinities of 2 probes to TSPO polymorphisms. Rat neuroinflammation models ( n=6) were established using lipopolysaccharide. Three days after modeling, small animal PET/CT imaging was performed using 18F-DPA-714 and 18F-TFQC, respectively, to observe and compare the uptake of the tracers, and the ratio of SUV mean of the right striatum to SUV mean of the left striatum (SUVR) was calculated. After the imaging, the expression and distribution of microglia and TSPO were detected by tissue immunofluorescence. Repeated-measures analysis of variance was used to analyze the SUVR data of different groups. Results:The inhibition constants ( Ki) of 18F-TFQC on 293T-LAB and 293T-HAB cells were 23.51 and 14.60 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 1.61, indicating low sensitivity to TSPO single nucleotide polymorphisms. The Ki of 18F-DPA-714 for binding to 293T-LAB and 293T-HAB cells were 45.23 and 6.47 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 6.99. Small animal PET/CT imaging demonstrated that specifically uptake of both probes could be found in neuroinflammatory lesions. The overall SUVR of 18F-DPA-714 in the lesions within 60minutes was slightly higher than that of 18F-TFQC, but no significant difference was observed ( F values: inter-group 0.40, time effect 0.30, cross-effect 0.03; all P>0.05). Conclusions:Compared with 18F-DPA-714, 18F-TFQC is less sensitive to TSPO gene polymorphisms, thus being more suitable for clinical application and promotion. It holds promise for the early identification of neuroinflammation and the efficacy monitoring of anti-inflammatory drug treatments.

Objective The study aimed to compare the efficacy and safety of tislelizumab combined with chemotherapy versus pembrolizumab combined with chemotherapy as first-line treatments for advanced lung squa-mous cell carcinoma.Methods We retrospectively reviewed and analyzed the medical records of 116 patients with advanced lung squamous cell carcinoma treated with first-line chemotherapy plus tislelizumab or pembrolizumab in Guangzhou Chest Hospital from September 2020 to April 2024.We focused on analysis of time to treatment failure(TTF)and objective response rate(ORR)as well as disease control rate(DCR)and treatment-related adverse events(TRAEs).Results At a median follow up of 19.7 monyhs,the median TTF was 9.7 months in the tislelizumab group and 7.7 months in the pembrolizumab group(P<0.05).In addition,the ORR in the tislelizumab group was significantly higher than that in the pembrolizumab group(77.6%vs.60.3%,P<0.05),with DCRs of 93.1%and 87.9%,respectively(P=0.342).Regarding safety,the proportions of grade 3 or higher TRAEs and any-grade TRAEs were comparable between the two groups:29.3%and 81.0%in the tislelizumab group,and 32.8%and 87.9%in the pembrolizumab group,respectively.The most common TRAEs in both groups were hematological toxicities.Conclusions Tislelizumab plus chemotherapy demonstrated better efficacy and safety compared to pembrolizumab with chemotherapy as first-line treatment for Chinese patients with advanced lung squamous cell carcinoma.

Objective:To explore the construction of management system of dynamic adjustment for supply catalogue of medical consumables based on diagnosis related groups(DRG),so as to realize the fine supervision and management of rational and compliant use for medical consumables.Methods:The management system of dynamic adjustment for supply catalogue of medical consumables was constructed from 6 dimensions(system establishment,hierarchical management,detailed classification,announcement management,strengthening trial and standardizing contract)through analyzed the existing problems.A total of 149 broad headings of using medical consumables in clinical work of Children's Hospital,Zhejiang University School of Medicine from January 2022 to December 2023 were selected.The changes of the ratio of hygienic material's income in medical income,and the ratio of hygienic material's cost in medically overall cost were compared between before adopted the management system of dynamic adjustment for supply catalogue of medical consumables(2022)and after adopted that(2023).Results:After dynamic adjustment,32 broad headings(21.48%)of 149 broad headings of medical consumables were adjusted according to trial process,and 14 broad headings(9.40%)of medical consumables were optimized in the secondary catalogue,and 85 broad headings(57.05%)of medical consumables reduced their product brand,and the use of 8(5.37%)broad headings of medical consumables were stopped.On the premise that both the person-time of outpatient and emergency,and the person-time of discharge increased,the ratio of the income of hygienic material in medical income decreased from 8.02%of 2022 to 7.29%of 2023,and the ratio of hygienic material cost in overall medical cost decreased from 15.38%of 2022 to 14.17%of 2023,and the accumulated cost of medical consumables was reduced by 7.37 million CNY,accounting for 4.1%of the expenditure of medical consumables.Online procurement rates of medical consumables were respectively 93.05%and 94.34%in 2022 and 2023,which showed an increasing trend year by year.Conclusion:The application of management system of dynamic adjustment for supply catalogue of medical consumables can reduce the ratio of consumables of hospital,and improve the management efficiency of medical consumables,and reduce the procurement cost of medical consumables.

Objective The study aimed to compare the efficacy and safety of tislelizumab combined with chemotherapy versus pembrolizumab combined with chemotherapy as first-line treatments for advanced lung squa-mous cell carcinoma.Methods We retrospectively reviewed and analyzed the medical records of 116 patients with advanced lung squamous cell carcinoma treated with first-line chemotherapy plus tislelizumab or pembrolizumab in Guangzhou Chest Hospital from September 2020 to April 2024.We focused on analysis of time to treatment failure(TTF)and objective response rate(ORR)as well as disease control rate(DCR)and treatment-related adverse events(TRAEs).Results At a median follow up of 19.7 monyhs,the median TTF was 9.7 months in the tislelizumab group and 7.7 months in the pembrolizumab group(P<0.05).In addition,the ORR in the tislelizumab group was significantly higher than that in the pembrolizumab group(77.6%vs.60.3%,P<0.05),with DCRs of 93.1%and 87.9%,respectively(P=0.342).Regarding safety,the proportions of grade 3 or higher TRAEs and any-grade TRAEs were comparable between the two groups:29.3%and 81.0%in the tislelizumab group,and 32.8%and 87.9%in the pembrolizumab group,respectively.The most common TRAEs in both groups were hematological toxicities.Conclusions Tislelizumab plus chemotherapy demonstrated better efficacy and safety compared to pembrolizumab with chemotherapy as first-line treatment for Chinese patients with advanced lung squamous cell carcinoma.

Objective:To explore the binding characteristics of N, N-diethyl-2-(2-(4-(2- 18F-fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-DPA-714) and ( R)- N-sec-butyl- N-methyl-4-(3-( 18F-trifluoromethyl)phenyl)quinazoline-2-carboxamide ( 18F-TFQC) to the single nucleotide polymorphisms of the 18×10 3 translocator protein (TSPO), and to evaluate the imaging efficacy and feasibility of those 2 molecular probes in neuroinflammation rat models. Methods:To test the selectivity of 18F-DPA-714 and 18F-TFQC for TSPO polymorphisms, the wild-type (high-affinity binding, HAB) and mutant (low-affinity binding, LAB) sequences of the human TSPO gene were transfected into 293T cells respectively. A competitive inhibition assay was carried out with N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)-3-isoquinoline carboxamide (PK11195) as an inhibitor to determine the binding affinities of 2 probes to TSPO polymorphisms. Rat neuroinflammation models ( n=6) were established using lipopolysaccharide. Three days after modeling, small animal PET/CT imaging was performed using 18F-DPA-714 and 18F-TFQC, respectively, to observe and compare the uptake of the tracers, and the ratio of SUV mean of the right striatum to SUV mean of the left striatum (SUVR) was calculated. After the imaging, the expression and distribution of microglia and TSPO were detected by tissue immunofluorescence. Repeated-measures analysis of variance was used to analyze the SUVR data of different groups. Results:The inhibition constants ( Ki) of 18F-TFQC on 293T-LAB and 293T-HAB cells were 23.51 and 14.60 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 1.61, indicating low sensitivity to TSPO single nucleotide polymorphisms. The Ki of 18F-DPA-714 for binding to 293T-LAB and 293T-HAB cells were 45.23 and 6.47 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 6.99. Small animal PET/CT imaging demonstrated that specifically uptake of both probes could be found in neuroinflammatory lesions. The overall SUVR of 18F-DPA-714 in the lesions within 60minutes was slightly higher than that of 18F-TFQC, but no significant difference was observed ( F values: inter-group 0.40, time effect 0.30, cross-effect 0.03; all P>0.05). Conclusions:Compared with 18F-DPA-714, 18F-TFQC is less sensitive to TSPO gene polymorphisms, thus being more suitable for clinical application and promotion. It holds promise for the early identification of neuroinflammation and the efficacy monitoring of anti-inflammatory drug treatments.

ObjectiveTo adapt the Stanford Expectations of Treatment Scale（SETS） into Chinese（C-SETS） and test the feasibility， validity and reliability of its application in patients with diarrhea-predominant irritable bowel syndrome（IBS-D） with liver-constraint and spleen-deficiency syndrome treated with traditional Chinese medicine（TCM）. MethodsWe obtained authorisation from the developer of the SETS， and followed the principle of "two-way translation" to translate the SETS by literal translation and back translation to form the C-SETS. Ninety-six IBS-D patients with liver-constraint and spleen-deficiency syndrome were enrolled as respondents and filled out C-SETS before receiving treatment； the feasibility was assessed by the recall rate， completion rate and the duration of filling out the scale； the reliability was assessed by Cronbach's α； the structural validity was assessed by exploratory and confirmatory factor analysis， and the content validity was assessed by correlation analysis. ResultsThe C-SETS consists of 10 items， with the 1st， 3rd， and 5th rating items constituting the Positive Expectations subscale， and the 2nd， 4th， and 6th rating items constituting the Negative Expectations subscale， each of which is rated on a 7-point Likert Scale. The recall of C-SETS was 100%（96/96）， the completion rate was 89.58%（86/96）； Cronbach's α for the Positive and Negative Treatment Expectations subscales were 0.845 and 0.854， respectively； exploratory factor analysis showed that the coefficient of commonality for all six entries was larger than 0.4， and that the six entries could be used by both factors to explain 77.092% of the total variance； validation factor analysis showed that the goodness-of-fit index， comparative fit index， root mean square of approximation error， canonical fit coefficient， and chi-square degrees of freedom ratio took the values of 0.943， 1.003， 0， 0.943， and 0.626， respectively； and the results of Spearman's analysis suggested that the C-SETS had good content validity. ConclusionThe C-SETS has well feasibility， reliability， and validity， which initially proves that it can be used as a tool to assess the treatment expectation of patients with IBS-D with liver-constraint and spleen-deficiency syndrome before receiving TCM treatment.

Objective To explore the influence of continuous thermal exposure on human cognitive performance.It provides solutions for the reduction of cognitive performance caused by high temperature emergency,and reduces the misoperation problems or even safety accidents of astronauts in high temperature emergency.Methods 14 right-handed male subjects were recruited and continuously exposed to four thermal environments of 32℃,35℃,38℃,and 41℃for 150 minutes,during which 5 different cognitive tasks(Posner Cueing Task,Deary-liewald Task,N-back Task,Wisconsin Card Task,Visual Search Task)were continuously performed to obtain relative cognitive performance.At the same time,a portable 2-lead holter was used to continuously capture ECG R signals during the cognitive test.Thereafter,the heart rate variability(HRV)analysis was conducted based on the ECG data,to explore the correlations between nonlinear indices(SD1,Shannon entropy,α2,D2)and the cognitive performance.Results Tresults showed that all nonlinear indexes changed with the exposure time and exposure temperature with certain patterns.In addition,through the correlation analysis between relative cognitive performance and nonlinear indicators,the most relevant indicator is α2(correlation coefficient 0.7).The correlation analysis results showed that the nonlinear index α2 had a U-shaped relationship with relative cognitive performance(correlation coefficient was 0.7).Based on that,a quantitative relationship between α2 and relative cognitive performance was obtained.It is found that when α2 was equal to 0.98,the worst relative cognitive performance was observed.Conclusion This study showed that the HRV nonlinear index α2 could serve as a reliable indicator of the cognitive performance of human during hot exposure,which provided a potential solution for the productivity and health evaluation of astronauts.

Objective:To investigate the etiology and prognosis of severe acute respiratory infection (SARI) in <5 year old outpatients.Methods:The data of 199 children with SARI admitted to the outpatient department of the Xi′an Children′s Hospital from January 2022 to December 2023 were included. Nasopharyngeal swabs were collected and the etiology of SARI virus in children was determined by polymerase chain reaction (PCR) within 48 h of study inclusion. The factors influencing respiratory support and length of stay in SARI children were analyzed by multiple linear regression.Results:Among the 199 patients included, 183 patients had positive nasopharyngeal swabs, with a positive rate of 92.0%. One pathogen was found in 124(62.3%) positive patients, two pathogens were found in 53(26.6%) positive patients, and three pathogens were found in 6(3.0%) positive patients. The most commonly detected viruses were rhinovirus (42.7%, 85/199), respiratory syncytial virus (33.2%, 66/199) and parainfluenza virus (14.1%, 28/199). Respiratory syncytial virus was detected in 40(54.8%) of the samples collected from infants aged 0 to 6 months, significantly higher than the frequency found in other age groups ( P<0.05). Adenoviruses were more common in the >12-24 month age group (22.0%). Age-specific weight Z score ( β=-0.223, 95% CI=-1.042--0.136, P=0.011) and SpO 2 ( β=-0.237, 95% CI=-0.21--0.037, P=0.006) were the influencing factors for respiratory support days in children with SARI. Age-specific weight Z score ( β=-0.223, 95% CI=-1.049--0.124, P=0.013) and SpO 2 ( β=-0.209, 95% CI=-0.204--0.020, P=0.017) were the factors influencing the length of hospital stay in SARI children. Conclusions:The findings of this study highlight the importance of viruses as SARI-associated pathogens in this population. Children at risk of a severe course of disease can be identified by measuring their age-specific weight Z score and SpO 2 on admission.