OBJECTIVE To conduct a comprehensive clinical evaluation of four nucleoside （acid） analogues that have been approved and marketed in China， such as entecavir， tenofovir disoproxil fumarate， tenofovir alafenamide fumarate， and tenofovir amibufenamide. METHODS According to the Guideline for the Administration of Clinical Comprehensive Evaluation of Drugs （2021 edition， trial implementation）， a comprehensive search was conducted across databases including CNKI， Wanfang Data， VIP， PubMed， the Cochrane Library， Embase， as well as relevant official websites. Drug package inserts， guidelines， consensus statements， and relevant literature for the four drugs were collected and subjected to a comprehensive evaluation across six dimensions： safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility. RESULTS The scores for entecavir in terms of safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility-along with its comprehensive score-were 13， 14， 13， 10， 18， and 6， totaling 74 points. For tenofovir disoproxil fumarate， the respective scores were 13， 17， 18， 8， 18， and 7， totaling 81 points. For tenofovir alafenamide fumarate， the scores were 14， 20， 12， 8， 18， and 5， totaling 77 points. Finally， for tenofovir amibufenamide， the scores were 10.5， 17， 10， 6， 15， and 4， totaling 62.5 points. CONCLUSIONS Tenofovir disoproxil fumarate， with the highest score， is recommended as the first-line option， suitable for adults， children， and pregnant women. However， caution is warranted for potential renal impairment. Tenofovir alafenamide fumarate is recommended as a second-line alternative， particularly for individuals at high risk for bone and renal damage. Entecavir has a score similar to tenofovir alafenamide fumarate but requires dosing on an empty stomach and dose adjustment based on renal function of patients. Tenofovir amibufenamide received the lowest score and is considered a weak recommendation. The clinical application of these nucleoside （acid） analogues should be individualized based on the patient’s age， physiological status， and risk factors.

Objective To assess the current status of microbial and parasitic quality control for laboratory animals in Jiangxi Province by analyzing microbiological and parasitic test results from production facilities between 2020 and 2024, and to provide a basis for enhancing quality control measures. MethodsIn accordance with the current national standards for laboratory animals at the time of testing, the Jiangxi Provincial Laboratory Animal Quality Inspection Station (affiliated to Institute of Occupational Medicine of Jiangxi) conducted microbial and parasitic testing on 451 laboratory animals of 4 species from 6 laboratory animal production units in Jiangxi Province between 2020 and 2024, and analyzed the quality status of laboratory animals in the province. ResultsPasteurella pneumotropica was detected in one mouse sample in 2020, with a detection rate of 5.00%. Pseudomonas aeruginosa was detected in one mouse sample and mouse hepatitis virus antibody was detected in another mouse sample in 2023, with a detection rate of 2.78%, respectively. No microorganisms or parasites that should be excluded from SPF grade mice as specified in the national standards were detected in 2021, 2022, or 2024, with a qualification rate of 100.00%. Pasteurella pneumotropica was detected in four rat samples in 2020, with a detection rate of 20.00%. Pseudomonas aeruginosa was detected in two rat samples in 2021, with a detection rate of 10.00%, and Tyzzer's disease agent antibody was detected in four rat samples in 2024, with a detection rate of 10.00%. No microorganisms or parasites that should be excluded from SPF grade rats as specified in the national standards were detected in 2022 or 2023, with a qualification rate of 100.00%. For rabbits and guinea pigs, no microorganisms or parasites required to be tested for conventional grade rabbits and guinea pigs as specified in the national standards were detected from 2020 to 2024, with the qualification rate of both species reaching 100.00%. ConclusionBased on the microbial and parasitic testing results, the quality of rabbits and guinea pigs in Jiangxi Province is satisfactory. However, some issues persist with rats and mice. It is recommended to enhance the quality of experimental animals in Jiangxi Province by increasing the frequency of random inspections by quality testing units or by improving the self-inspection capabilities of production and user facilities.

OBJECTIVE To provide references for the accurate identification and management of immune-related cutaneous adverse events （irCAEs） caused by durvalumab， and ensuring safe clinical drug use. METHODS Clinical pharmacists participated in the diagnosis and treatment process of a patient with gallbladder cancer who developed irCAEs caused by durvalumab. The clinical pharmacists systematically reviewed the patient’s past medical history and medication history， and assisted physicians in assessing the association between adverse drug reactions and administered drugs. Meanwhile， the clinical pharmacists conducted a graded assessment of the adverse reaction， proposed recommendations such as discontinuing durvalumab and adjusting the administration regimen of glucocorticoids， assisted physicians in restarting immunotherapy， and carried out medication education and other pharmaceutical care. RESULTS The occurrence of irCAEs in this patient was “highly likely” related to durvalumab and was classified as severe. The physicians adopted the clinical pharmacist’s opinion， and after symptomatic treatment， the patient’s skin symptoms improved， and discharged with medication. After the completion of glucocorticoid therapy for the patient， the physician restarted immunotherapy with tislelizumab， and no related adverse reactions occurred again in the patient. CONCLUSIONS Durvalumab can cause irCAEs such as severe skin maculopapular rash. In clinical practice， it is crucial to promptly identify and discontinue suspicious drugs， immediately implement effective symptomatic treatment measures， and actively resume immunotherapy to ensure the continuity and safety of the patient’s treatment.

Objective To investigate the correlation between seasonal blood pressure （BP） variability and total burden score of cerebral small vessel disease （CSVD） with different severities. Methods The patients with CSVD who were consecutively admitted were enrolled， and according to the total burden score based on head MRI， they were divided into control group （CSVD 0 points）， mild group （CSVD 1‒2 points）， and moderate-to-severe group （CSVD 3‒4 points）.General information was collected from all patients， as well as 24-hour ambulatory blood pressure monitoring （ABPM） during warm and cold seasons. The correlation between ABPM parameters in different seasons and the imaging burden of different severities of CSVD was analyzed. Results A total of 145 patients were enrolled， with 29 patients in the control group，64 in the mild group， and 52 in the moderate-to-severe group.Compared with the control group， the mild group and the moderate-to-severe group had significantly higher age（F=9.721，P=0.001）， 24-hour systolic blood pressure （SBP） in hot season（F=6.572，P=0.002）， daytime SBP in hot season（F=6.460，P=0.002）， daytime diastolic blood pressure （DBP） in hot season（F=5.802，P=0.004）， nighttime SBP in hot season（F=8.508，P<0.001）. Compared with the control group， the moderate-to-severe group had significantly higher levels of 24-hour DBP in hot season（F=4.564，P=0.012）， nighttime DBP in hot season（F=6.294，P=0.002），24-hour SBP in cold season（F=7.012，P=0.001）， 24-hour DBP in cold season（F=4.527，P=0.012），daytime SBP in cold season（F=5.708，P=0.004），daytime DBP in cold season（F=3.138，P=0.046），nighttime SBP in cold season（F=9.154，P<0.001）， and nighttime DBP in cold season（F=8.006，P=0.001）. Compared with the control group， the mild group and the moderate-to-severe group had a significantly higher proportion of patients with abnormal BP circadian rhythm in hot season （χ2=13.059，P=0.001） and cold season （χ2=10.091，P=0.006）.The ordinal logistic regression analysis showed that age （OR=1.147， 95%CI 1.084‒1.214） was an independent risk factor for CSVD， and compared with the patients with dipper-type blood pressure in hot season， the patients with non-dipper blood pressure pattern had a risk of CSVD increased by 13.282 times （OR=13.282， 95% CI 2.379‒74.159）， while those with reverse-dipper blood pressure pattern had a risk of CSVD increased by 25.569 times（OR=25.569，95%CI 3.061‒213.551）. Conclusion The imaging burden score of CSVD increases with the increase in age and the proportion of abnormal circadian blood pressure pattern in hot season， and both age and abnormal circadian blood pressure pattern in hot season are independent risk factors for the imaging burden of CSVD.

Objective: To explore the association of vegetables and fruits intake with depressive symptoms among multi ethnic first year junior high school students in Yunnan Province, so as to provide data support for preventing and reducing depressive symptoms among first year junior high school students. Methods: From October to December 2022, a cluster random sampling method was used to select 8 500 first year junior high school students from 11 ethnic minority areas in Yunnan Province (Fugong County, Longling County, Longyang District, Luchun County, Mojiang County, Nanjian County, Qiaojia County, Shuangjiang County, Tengchong City, Yuanmou County, Zhenyuan County), to investigate with a questionnaire. The Dietary Frequency Questionnaire was used to collect dietary behavior datas, and the Chinese version of Depression Anxiety Stress Scale-21 (DASS-21) was used to assess depressive symptoms. The generalized linear model was used to analyze the association of vegetable and fruit intake with depressive symptoms in students, and stratified analysis was performed according to ethnicity. Results: The detection rate of depressive symptoms among first year junior high school students in Yunnan Province was 29.5%. The detection rates of depressive symptoms in Han and minority first year junior high school students were 26.9% and 31.6%. After controlling for demographic variables such as gender, age, family residence and other confounding factors, the generalized linear model analysis results showed that the intake of leafy vegetables ( β= -0.07 , 95%CI =-0.12 to -0.01), flat fruits ( β=-0.06, 95%CI =-0.12 to -0.00) and hot natured fruits ( β=0.11, 95%CI = 0.04- 0.17) were associated with depressive symptoms in Han first year junior high school students (all P <0.05). The intake of melon and fruit vegetables ( β=-0.06, 95%CI =-0.11 to -0.01) and hot natured fruits ( β=0.06, 95%CI =0.01-0.12) were associated with depressive symptoms in ethnic minority first year junior high school students (both P <0.05). Conclusions The intake of vegetables and fruits among multi ethnic first year junior high school students in Yunnan Province is related to the risk of depressive symptoms. It is suggested to strengthen the consumption guidance and education of vegetables and fruits to prevent depressive symptoms among first year junior high school students.

Objective To analyze the epidemiological characteristics of hand, foot, and mouth disease (HFMD) in Shanxi Province from 2012 to 2024, and predict the incidence trend for 2025, and to provide a scientific basis for the formulation of prevention and control strategies. Methods Based on the surveillance data of HFMD in Shanxi Province from 2012 to 2024, the spatial and temporal distribution characteristics and time trends of the disease were analyzed. The ARIMA model was constructed and used to predict the incidence trend in 2025. Results From 2012 to 2024, a total of 254 028 HFMD cases were reported in Shanxi Province, with an average annual incidence rate of 54.17 per 100 000 population, a severe case rate of 0.56%, and a case fatality rate (CFR) of 12.60 per 100 000 population. Joinpoint regression analysis showed that the incidence rate, severe case rate, mortality rate, and case fatality rate all presented a downward trend. The epidemic exhibited obvious seasonal distribution characteristics, with the peak period from April to November, and two incidence peaks in June-July and October-November. The male-to-female incidence ratio was 1.41:1. Children aged 1-5 years accounted for 89.24% of the total cases, among which scattered children (58.48%) and nursery children (33.54%) were the high-risk groups. Linfen City (96.06 /100 000) and Taiyuan City (88.54 /100 000) had relatively high incidence rates. After 2017, the proportion of enterovirus A71 (EV-A71) decreased, while coxsackievirus A16 (Cox-A16) and other enteroviruses became the main epidemic strains. The ARIMA(1,0,1)(0,1,1)₁₂ model predicted that the incidence of HFMD in 2025 would remain at the level of 2023-2024, and the dual-peak characteristic would continue. Conclusion From 2012 to 2024, the overall HFMD epidemic in Shanxi Province generally shows a significant downward trend. The high-risk population includes scattered children and nursery children under 5 years old, with high-incidence areas concentrated in the central and southern regions, requiring focused attention. The seasonal ARIMA model can effectively fit the evolutionary trend of HFMD incidence in Shanxi Province and possesses short-term predictive capability.

Objective To investigate the incidence and adverse prognosis of late onset sepsis(LOS)in neonates in neonatal intensive care unit(NICU).Methods A retrospective study was conducted to collect and analyze the peri-natal condition,underlying diseases,invasive procedures,and adverse prognosis of neonates in NICU of a regional maternal and child healthcare hospital from 2019 to 2023.According to whether LOS occurred during hospitaliza-tion,neonates were divided into LOS group and non-LOS group.The LOS group was divided into 5 subgroups based on whether invasive procedures were performed:LOS plus umbilical vein catheter(UVC)group,LOS plus peripherally inserted central catheter(PICC)group,LOS plus sequential catheter group,LOS plus tracheal intuba-tion group,and LOS plus lumbar puncture group,the relationship between LOS and adverse prognosis was ana-lyzed.Results Among 2 945 neonates in NICU,354(12.02％)developed LOS.Comparison between LOS groups and non-LOS group were as follows:in term of perinatal condition of neonates,there were statistically significant difference in weight,gestational age,and whether they were twins between the two groups(all P＜0.001);in term of underlying diseases,there were statistically significant differences in the number of cases of maternal gestational hypertension,neonatal asphyxia,neonatal congenital heart disease,neonatal ventricular dilation,neonatal pneumo-nia,neonatal hyperthyrotropinemia,and neonatal anemia,as well as five invasive procedures between the two groups(all P＜0.05).Compared with the non-LOS group,the incidences of retinopathy of prematurity(ROP),neonatal necrotizing enterocolitis(NNEC),bronchopulmonary dysplasia(BPD),and neonatal respiratory distress syndrome(NRDS)in LOS group were all higher(all P＜0.001).Regression analysis showed that compared with the non-LOS groups,the risk of ROP increased in the LOS group and its subgroups,with the LOS plus sequential catheter group having a 2.27-fold higher risk of ROP than non-LOS group;the risk of NNEC increased in the LOS group and its subgroups,with the LOS plus UVC group having an 8.29-fold higher risk of NNEC than the non-LOS group.Except for the LOS plus UVC group,the risk of BPD increased in the LOS group and other subgroups,with the LOS plus PICC group and LOS plus sequential catheter group having 4.68-and 4.64-fold higher risk of BPD than the non-LOS group,respectively;the risk of NRDS in the LOS plus PICC group was 6.84-fold higher than the non-LOS group(all P＜0.05).The top three pathogens causing LOS were coagulase negative Staphylococcus,Klebsiella pneumoniae,and Escherichia coli.Conclusion LOS can significantly increase the risks of ROP,NNEC,BPD,and NRDS.LOS plus invasive procedures can further increase the risk of adverse prognosis.

Objective:To analyze the clinical blood bile acid spectrum detection results of patients with biliary atresia（BA）and non-BA cholestasis,and to clarify the distribution changes of major bile acids in the serum of BA patients and their potential differential diagnostic value.Methods:The serum bile acid concentrations of BA and other non-BA cholestasis patients in the same age who underwent clinical bile acid spectrum testing at Children's Hospital of Fudan University from September 2019 to September 2020 were retrospectively analyzed.Non-BA patients were divided into the low gamma-glutamyl transpeptidase (GGT) cholestasis group (33 cases) and the high GGT cholestasis group (19 cases) based on serum GGT levels.ROC curve was used to analyze the differences in bile acid concentration levels between BA and non-BA patients,and their potential differential diagnostic value for BA.Results:(1) A clinical bile acid spectrum was collected from 74 BA patients and 52 non-BA patients.The median level of primary bile acid concentration in the BA group increased,ranging from 4.8 to 46.7 times the upper limit of the normal reference value.In the BA group,the median levels of all secondary bile acid concentrations decreased,ranging from 1/660 to 1/1.1 of the upper limit of the normal reference value.(2) The concentrations of glycocholic acid(GCA) and taurocholate (TCA) in the BA group were higher than those in the high GGT cholestasis group and the low GGT cholestasis group( P<0.05).(3) ROC curve analysis showed that when the GCA concentration>8 690 nmol/L,the AUC value was 0.706 (95% CI 0.609-0.803),with a sensitivity of 0.811,specificity of 0.538,positive predictive value of 0.714,and negative predictive value of 0.667. Conclusion:An obstruction of bile salt secretion in the bile duct,leading to a decrease in secondary bile acid production in the intestine.A significant decrease in secondary bile acid levels,accompanied by a significant increase in GCA concentration may suggest BA.

BACKGROUND:In previous studies,the equivalent structure of three-dimensional cell reconstruction of tissue engineering oral mucosa is similar to normal oral mucosa,including epithelial-like structure,lamina propria-like structure,and vascular lumen-like structure,and has initially achieved the establishment of vascular equivalent,but its vascularization characteristics are not very clear.OBJECTIVE:Vascular-like structures of vascularized oral mucosa equivalent were obtained by targeting vascular endothelial cells specific marker expression profiles correlated with laser capture microdissection system,and their vascularization ability was evaluated to reveal their vascularization characteristics.METHODS:Human gingival epithelial cells were cultured from human gingival epithelium and human gingival fibroblasts,human gingival mesenchymal stem cells were cultured from human gingival lamina propria.Human gingival mesenchymal stem cells were induced to differentiate into vascular endothelial-like cells after monoclonal expansion culture.Human gingival epithelial cells,human gingival fibroblasts,and vascular endothelial-like cells were loaded with acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold to construct the vascularized oral mucosa equivalent.The layered structure of oral mucosa equivalent(experimental group)and the acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold(control group)were implanted subcutaneously into the back of nude mice,respectively.14 days later,the incision surface of the two groups was coated with biogel.The biogel surface of the experimental group was inoculated with human gingival epithelial cells,while the control group was not inoculated with cells.The samples were collected after 14 days of feeding.The layered structure of oral mucosa equivalent was observed by morphology.The neovascular-like structures in oral mucosa equivalents were labeled by immunohistochemistry and immunofluorescence with a more comprehensive expression profile of vascular endothelial cells,and the vascularization characteristics were analyzed.A laser capture microdissection system was used to capture the neovascularization structures in the oral mucosa equivalents specifically labeled by immunohistochemistry and analyze their vascularization characteristics.RESULTS AND CONCLUSION:(1)The morphology showed that the cell level of oral mucosa equivalent was clear,and the structure was similar to that of normal oral mucosa,that is,there were epithelioid structures,lamina-like structures,and vascular cavelike structures,and there were scattered erythrocytes in the vascular cavelike structures.(2)The results of EdU Apollo tracer seed cells in the oral mucosa equivalent group showed that human gingival epithelial cells labeled with EdU Apollo 488 showed green fluorescence expression.DAPI labeled human gingival fibroblasts showed blue fluorescence expression and formed lamina-like structures in vivo.EdU Apollo 567 labeled vascular endothelial-like cells showed red fluorescence expression and formed a vascular-like structure in vivo.(3)Vascular endothelial cell specific marker expression profile immunofluorescence labeling of vascular structure showed that compared with normal oral mucosa,the expressions of CD31,CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 in oral mucosa equivalents were increased(P<0.000 1).There were no significant changes in CD34 expression(P>0.05).(4)Compared with the specifically labeled oral mucosal vascular structures,the expression levels of CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 of the oral mucosa equivalents targeted by the laser capture microdissection system were increased(P<0.000 1).There were no significant changes in expression of CD31 and CD34(P>0.05).(5)The results showed that the oral mucosa equivalent reconstructed by three-dimensional cell stratification could achieve good vascularization,and its vascularization characteristics were consistent with the immunological function and characteristics of neovascularization.Vascularization helps three-dimensional cell layer reconstruction of oral mucosa equivalent regeneration.

[Purpose]To analyze the lifetime risk of developing and dying from lung cancer at global and regional levels.[Methods]Data of lung cancer incidence and mortality were obtained from GLOBOCAN 2022 and the population and all-cause mortality data were obtained from the United Nations.The lifetime risk of developing and dying from lung cancer globally and across different regions was estimated by multiple primary adjustment method.[Results]The global lifetime risk of developing lung cancer was 3.59％[95％confidence interval(CI):3.58％～3.59％],ranking third among all cancer types.There were significant gender and regional differences in lifetime risk values.The risk for male was 4.43％(95％CI:4.42％～4.44％),which was higher than that for female(2.71％,95％CI:2.70％～2.72％),with a male-to-female ratio of 1.63.Among regions with varying human development index(HDI)levels,the risk increased with HDI levels,in very high HDI re-gions risk was 5.36％(95％CI:5.34％～5.37％),while in low HDI regions the risk was 0.34％(95％CI:0.33％～0.34％).Among the 20 global regions,East Asia had the highest lifetime risk of 7.53％(95％CI:7.52％～7.55％),while West Africa had the lowest risk of 0.16％(95％CI:0.16％～0.17％).The global lifetime risk of dying from lung cancer was 2.78％(95％CI:2.78％～2.78％),ranking the first among all cancer types.There were significant sex and regional differ-ences in lifetime death risk values.The risk for male was 3.64％(95％CI:3.63％～3.64％),which was higher than that for female(1.89％,95％CI:1.89％～1.90％),with a male-to-female ratio of 1.93.Among regions with varying HDI levels,the risk increased with HDI levels,in very high HDI re-gions the risk was 3.98％(95％CI:3.97％～3.99％),while in low HDI regions the risk was 0.31％(95％CI:0.31％～0.31％).Among the 20 global regions,the Federated States of Micronesia/Poly-nesia had the highest death risk of 5.80％(95％CI:4.98％～6.62％),while West Africa had the lowest risk of 0.15％(95％CI:0.15％～0.16％).The lifetime risk of developing and dying from lung cancer in China was 7.54％(95％CI:7.52％～7.56％)and 5.88％(95％CI:5.87％～5.90％),respec-tively,both ranking the first among all cancer types.[Conclusion]The lifetime risk of developing and dying from lung cancer remains high globally and across different regions,with a particularly heavy burden in high-HDI areas.In China,both the lifetime risk of developing and dying from lung cancer are higher than the global average.This highlights the need for continued enhance-ment of comprehensive prevention and control measures,including addressing lung cancer-related risk factors,as well as improving screening,early diagnosis,and treatment efforts to reduce the lung cancer burden.