Objective To analyze the risk of adverse drug events in pediatric clinical applications of tocilizumab versus inflixima.Methods Adverse event(AE)reporting data for tocilizumab versus infliximab in the U.S.Food and Drug Administration Adverse Event Reporting System database for the pediatric population from Q1 2013 to Q1 2023 were collected.AE risk signal mining was performed using the reporting odds ratio(ROR)method and the proportional reporting ratio(PRR)method.AEs were also classified and statistically analyzed according to the preferred system organ classification and preferred terminology(PT)of the International Dictionary of Medical Terminology.Results Data were extracted and cleaned to include 1 052 AE reports with 198 positive PT signals for tocilizumab as the suspected drug and 9 1 39 AE reports with 387 positive PT signals for infliximab as the suspected drug.The analyses suggested that the stronger positive risk signals for both drugs were focused on gastrointestinal disorders,infectious and invasive diseases,laboratory tests,musculoskeletal and connective tissue disorders,and blood,vascular,and lymphatic disorders.The risk signals for infliximab were focused on gastrointestinal disorders,infections,and infectious diseases,while the risk signals for tocilizumab were focused on the musculoskeletal muscle system.Conclusion Clinical use of both drugs in children has multi-system effects,tocilizumab may have effects on growth and development,and infliximab has effects on the gastrointestinal tract in children.

Objective: To investigate the causal relationship between antioxidant nutrients and pregnancy complications, so as to provide the reference for the prevention and treatment of pregnancy complications. Methods: Data of seven antioxidant nutrients including vitamin A, vitamin C, vitamin E, selenium, zinc, copper and iron were collected from genome-wide association study (GWAS) Catalog database, and data of four pregnancy complications including gestational diabetes mellitus, pre-eclampsia, spontaneous abortion and preterm birth were collected from the Finland database. Single nucleotide polymorphism (SNP) data were collected, and 27 SNPS strongly correlated with seven antioxidant nutrients were selected as instrumental variables. Mendelian randomization (MR) analyses were performed using the inverse-variance weighted (IVW) method with seven antioxidant nutrients as exposures factors and four pregnancy complications as outcome variables. The heterogeneity was assessed using the Cochran's Q test, the horizontal pleiotropy was assessed using the MR-PRESSO test and MR-Egger regression, and the robustness of the results was verified with the leave-one-out. Results: Cochran's Q test showed heterogeneity of MR results between vitamin C and gestational diabetes mellitus, preeclampsia and preterm birth, between vitamin E and iron and gestational diabetes (all P<0.05), and a random effect model was employed. There was no heterogeneity in other results (all P>0.05), and a fixed effect model was employed. MR analysis results showed that there was no causal association between seven antioxidant nutrients and the risk of four pregnancy complications (all P>0.05). MR-PRESSO test and the MR-Egger regression identified no horizontal pleiotropy of instrumental variables (both P>0.05). Conclusion This study did not find genetically predicted associations of antioxidant nutrients with pregnancy complications.

Background The mental health problems of employees in administrative organs and public institutions are highly valued.However,there is a lack of understanding regarding the mental health status of employees in provincial and municipal administrative organs and public institutions in Qinghai region.Objective To analyze the anxiety and depression of employees in provincial and municipal administrative organs and public institutions in Qinghai region,so as to provide references for promoting their mental health and intervening in psychological problems.Methods From October 23 to 28,2022,a total of 3 096 employees in provincial and municipal administrative organs and public institutions in Qinghai region were enrolled using stratified cluster sampling technique,and were assessed using Self-rating Anxiety Scale(SAS)and Self-rating Depression Scale(SDS).Results A total of 1797(58.04％)employees in municipal and above administrative organs and public institutions in Qinghai region completed a valid questionnaire survey.Depressive symptoms were noted in 579(32.22％).SDS scores yielded statistical difference among the selected employees of different ethnicities,types of job positions and educational levels(F=9.074,101.488,4.477,P<0.01),and the severity of depressive symptoms also demonstrated statistical difference among the selected employees with different ethnicities,educational levels and types of job positions(H=49.196,17.028,160.848,P<0.01).Anxiety symptoms were detected in 711(39.57％)employees.SAS scores exhibited statistical difference among the employees with different genders,ages,ethnicities,educational levels,marital status and types of job positions(t=-4.571,F=6.648,3.950,5.243,12.008,22.253,P<0.01).Statistical differences were also illustrated in the severity of anxiety symptoms among the selected employees with different ages,genders,ethnicities,educational levels,marital status and types of job positions(H=24.361,-3.788,28.365,24.268,25.976,56.204,P<0.01).Conclusion About one-third of employees in municipal and above administrative organs and public institutions in Qinghai region may have symptoms of depression and anxiety.The depression symptoms are more severe among Tibetan people,those with low education levels and ordinary civil servants.The anxiety symptoms are more severe among employees aged 30 and below,those with low education levels,unmarried and those in technical positions.

AIM:To explore the roles and associations of hepatocyte nuclear factor 4 alpha(HNF4A)and mu-protocadherin(MUCDHL)in the kidney of diabetic mice.METHODS:(1)A cohort of six 12-week-old db/m mice and six db/db mice were selected and maintained on a standard diet until 16 weeks.The protein levels of fibronectin(FN),collagen type III(Col-III),E-cadherin,α-smooth muscle actin(α-SMA),HNF4A,Snail and MUCDHL in renal tissues were scrutinized using Western blot.Immunohistochemical staining was conducted to observe the distribution and expres-sion of FN,HNF4A and MUCDHL.(2)Mouse renal tubular epithelial cells(mRTEC)were cultured in vitro and catego-rized into groups:normal glucose(NG)group,high glucose(HG)group,overexpression control groups(NG+vector and HG+vector),overexpression groups(NG+OE-MUCDHL,HG+OE-MUCDHL,NG+OE-HNF4A and HG+OE-HNF4A),knockdown control groups(NG+control and HG+control),and knockdown groups(NG+si-MUCDHL,HG+si-MUCDHL,NG+si-HNF4A and HG+si-HNF4A).The relevant protein levels were also detected by Western blot.RESULTS:(1)In db/db group,elevated body weight,blood glucose and urine albumin-to-creatinine ratio(UACR)indicated significant re-nal injury.Compared with db/m group,the mice in db/db group exhibited increased expression of FN,Col-III,α-SMA and Snail,and decreased expression of E-cadherin,HNF4A and MUCDHL.MUCDHL was predominantly expressed in the apical membrane of renal tubular epithelial cells,FN in the tubular mesenchyme,and HNF4A in the plasma and nu-cleus of renal tubular cells.(2)In HG group,there was an up-regulation in the expression of fibrosis-related proteins and a down-regulation in the expression of E-cadherin,HNF4A and MUCDHL compared with NG group.Overexpression of MUCDHL led to a decrease in the expression of FN,Col-III,α-SMA and Snail proteins,an increase in the expression of E-cadherin and MUCDHL proteins,and unaltered expression of HNF4A.Knockdown of MUCDHL resulted in a reversal of the aforementioned effects,with HNF4A expression remaining unaltered.Overexpression of HNF4A led to an increased ex-pression of MUCDHL,and the expression changes of the remaining indicators were consistent with the overexpression of MUCDHL.Knockdown of HNF4A reversed the aforementioned effects.MUCDHL may represent a downstream target gene of HNF4A.CONCLUSION:The diminished expression of HNF4A and MUCDHL in the renal tubules of diabetic mice implies their involvement in the progression of renal fibrosis in diabetic kidney disease(DKD).HNF4A may potentially impede the progression of renal fibrosis in DKD by up-regulating the expression of MUCDHL.

Objective To analyze the correlation between T lymphocyte subsets,neutrophil/lymphocyte ratio(NLR),procalcitonin(PCT)and the severity of sepsis.Methods A prospective research method was adopted.A total of 78 sepsis patients admitted to the department of intensive care medicine of Zibo Central Hospital from January 2021 to December 2022 were selected as the research subjects.Patients were divided into a septic shock group(37 cases)and a sepsis group(41 cases)based on the severity of their condition,with 40 healthy examinees from our hospital as the healthy control group.Using flow cytometry to measure the levels of CD4+ T lymphocytes count(CD4+ T)and CD8+ T lymphocytes count(CD8+ T)in three groups of subjects,calculate the CD4+ T/CD8+ T lymphocyte ratio(CD4+ T/CD8+ T)and NLR.The levels of PCT and interleukin-6(IL-6)were measured using electrochemiluminescence immunoassay,and the levels of C-reactive protein(CRP)were measured using immunoassay turbidimetry.Acute physiology and chronic health evaluationⅡ(APACHEⅡ)score within 24 hours was recorded for the two groups of patients,and the differences in lymphocyte subsets and various inflammatory indicators were compared between the groups.Pearson correlation analysis was used to analyze the correlation between various indicators and APACHEⅡscore.Results The CD4+ T,CD8+ T,and CD4+T/CD8+T levels in the septic shock and sepsis groups were significantly lower than those in the healthy control group[CD4+ T(×106/L):168.27±76.68,266.08±131.57 vs.789.60±173.78,CD8+ T(×106/L):156.50±68.37,205.81±75.60 vs.636.42±90.59,CD4+ T/CD8+ T:1.09±0.39,1.27±0.34 vs.1.44±0.38,all P<0.01],NLR,PCT,CRP and IL-6 were significantly higher than those in the healthy control group[NLR:25.85±11.62,15.94±8.72 vs.2.68±1.31,PCT(μg/L):21.82±15.28,9.09±4.96 vs.0.13±0.10,CRP(mg/L):158.65±62.33,106.97±51.49 vs.6.48±2.08,IL-6(ng/L):1 344.64±899.21,245.31±176.99 vs.3.25±1.83,all P<0.01].The APACHEⅡscore in the septic shock group was significantly higher than that in the sepsis group(32.00±1.00 vs.22.01±1.09,P<0.05).Correlation analysis showed that the levels of CD4+ T,CD8+ T,CD4+ T/CD8+ T in two groups of sepsis patients were negatively correlated with the APACHEⅡscore(r values were-0.571,-0.506,and-0.555,respectively,all P<0.01),while the levels of NLR,PCT,CRP,and IL-6 were positively correlated with the APACHEⅡscore(r values were 0.711,0.709,0.777,and 0.707,respectively,all P<0.01).Conclusions As the levels of T lymphocyte subsets decrease,inflammatory indicators like NLR and PCT rise,indicating a more severe sepsis condition.Therefore,T lymphocyte subsets and levels of various inflammatory indicators can serve as markers for evaluating the severity of sepsis.

Radiotherapy is one of the main treatment methods for malignant tumors, which can cause the radiation damage to normal tissues. Radiation-induced skin injury (RISI) is one of the main adverse reactions caused by radiotherapy. The main clinical manifestations of RISI are dermatitis, ulcer, erosion and necrosis, which seriously affect the quality of life and treatment effect of tumor radiotherapy patients, and even affect the overall survival of patients. The pathological mechanism of RISI is still unclear. Some studies have shown that inflammation and oxidative stress are the main causes of RISI. RISI can be divided into acute and chronic RISI according to the different onset time, and different treatment strategies can be formulated according to the severity of the injury. In this article, clinical manifestations, classification, pathogenesis, prevention and treatment of RISI are comprehensively summarized.

Objective To investigate the correlation of cerebral blood flow(CBF)after thrombolys-is with ischemia-reperfusion(I/R)injury and neurological function in patients with acute ischemic stroke(AIS).Methods Clinical data of 150 AIS patients admitted to our department from Febru-ary 2021 to February 2024 were collected and analyzed retrospectively.According to the changes in CBF in the affected side after thrombolysis,they were divided into hyperperfusion group(48 cases)and hypoperfusion group(102 cases).The condition of hemorrhagic transformation and perfusion parameters included CBF,cerebral blood volume(CBV),time to peak of residual func-tion(Tmax),mean transit time(MTT)and time to peak(TTP),and the relative values of regional cerebral blood flow(rCBF),rCBV,Tr,max,rMTT and rTTP.The general clinical data,oxidative stress,NIHSS score and inflammatory factor levels were compared between the two groups.Pear-son/Spearman correlation analysis was used to analyze the correlation between rCBF and oxida-tive stress,inflammatory factors,hemorrhagic transformation and NIHSS score in AIS patients after thrombolysis.Results In the hypoperfusion group,the MTT,Tmax and TTP values were sig-nificantly higher,and the CBF value was obviously lower in the affected side than the healthy side(P＜0.01).In hyperperfusion group,the MTT and TTP were notably lower,while the CBF and CBV were remarkably higher in the affected side than the healthy side(P＜0.01).The hypoperfu-sion group had significantly higher rMTT,Tr,max and rTTP,but lower rCBV and rCBF than the hyperperfusion group(P＜0.01).The levels of malondialdehyde(MDA),advanced oxidation pro-tein products,TNF-α and C-reactive protein(CRP)were significantly lower,and the level of su-peroxide dismutase(SOD)was higher in the hypoperfusion group than the hyperperfusion group(P＜0.05,P＜0.01).Pearson correlation analysis showed that rCBF was negatively correlated with MDA and TNF-α(r=-0.436,r=-0.451,P＜0.01)and positively correlated with SOD(r=0.412,P＜0.01).Conclusion The CBF changes after thrombolysis in AIS patients have a good correlation with I/R injury,but not with the recovery of neurological function.

To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.
Humans ; Dermatitis, Atopic/drug therapy* ; Quality of Life ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Objective:To investigate the distribution of iron deposition in the substantia nigral (SN) subregions on quantitative susceptibility mapping (QSM) and the change of swallow tail sign (STS) in patients with relapsing-remitting multiple sclerosis (RRMS) of different disease stages.Methods:The clinical and imaging data of 53 patients with RRMS (case group) diagnosed at the First Hospital of Chongqing Medical University from November 2019 to December 2021 were retrospectively analyzed. The case group was divided into 0-5 years subgroup, 6-10 years subgroup, and >10 years subgroup according to the disease duration; another 37 age-and gender-matched healthy volunteers were recruited as the control group during the same period. All subjects underwent MRI and QSM reconstruction. First, the SN was divided into four subregions: rostral anterior-SN (aSNr), rostral posterior-SN (pSNr), caudal anterior-SN (aSNc), and caudal posterior-SN (pSNc) on the QSM, and the quantitative susceptibility value (QSV) of each subregion was measured, and then the STS of the SN was observed and scored on the susceptibility weighted imaging (SWI) generated by post-processing. ANOVA was used to compare the differences in the QSV of each subregion of SN among the groups, and the probability of abnormal STS was compared using the χ 2 test. Spearman′s test was used to analyze the correlation between the QSV of each subregion of SN and the STS score. Results:The differences in QSV of aSNr, pSNr, aSNc, and pSNc were statistically significant among the 0-5 years subgroup, 6-10 years subgroup,>10 years subgroup of RRMS patients and the control group ( P<0.05). The QSV of aSNr, pSNr, and aSNc in 0-5 years subgroup was higher than those in the control group ( P was 0.039, 0.008, 0.039, respectively). The QSV of aSNr, aSNc, and pSNc in the 6-10 years subgroup were higher than those in the 0-5 years subgroup ( P was <0.001, 0.020, 0.015, respectively). The QSV of the aSNc, pSNc in >10 years subgroup were lower than those in the 6-10 years subgroup ( P=0.037, 0.006). The QSV of aSNr, pSNr in >10 years subgroup were higher than those in the control group ( P was <0.001, 0.001). There were 7 cases of abnormal STS in the 0-5 years subgroup, 11 cases in the 6-10 years subgroup, 12 cases in >10 years subgroup, and 9 cases in the control subgroup, and there was a statistically significant difference in the probability of abnormal STS among the subgroups of the RRMS patients and the control subgroup (χ 2=16.20, P=0.011). Both the scores of STS in the 6-10 years subgroup and >10 years group were positively correlated with the QSV in pSNc ( r s=0.65, P=0.006; r s=0.48, P=0.045). Conclusions:In RRMS patients, SN iron deposition is concentrated on aSNr, pSNr, and aSNc in the 0-5 years subgroup and on aSNr, aSNc and pSNc in the 6-10 years subgroup. The QSVs of all SN subregions have a downward trend in >10 years subgroup compared with that in the 6-10 years subgroup. Both the QSVs of the pSNc in the 6-10 years group and >10 years group are positively related to STS scores. These help explore the potential progression pattern of SN iron deposition in RRMS patients and the cause of abnormal STS in RRMS patients.

Purpose/Significance The current situation of internet diagnosis and treatment in medical institutions in Beijing is ana-lyzed and studied to provide references for further promoting internet diagnosis and treatment and improving supervision of internet diagno-sis and treatment in medical institutions.Method/Process By using the methods of literature analysis,questionnaire survey and on-site interview,the current situation of internet diagnosis and treatment in medical institutions that have been qualified for internet diagnosis and treatment in Beijing is investigated.Result/Conclusion The internet diagnosis and treatment has been attached great importance by medical institutions in Beijing and has developed rapidly.However,it is also necessary to further optimize the internal and external envi-ronment for the development of internet diagnosis and treatment,strengthen supervision,and improve the public's acceptance.