Objective:To investigate the causal impact of maternal smoking around birth(MSAB)on off-spring's risk of attention deficit hyperactivity disorder(ADHD),autism spectrum disorder(ASD),bipolar disorder(BD),and major depressive disorder(MDD).Methods:The datasets for MSAB and 4 psychiatric disorders were extracted from genome-wide association studies(GWAS).Mendelian randomization(MR)was employed,using in-verse variance weighting(IVW)as the primary analysis method.Sensitivity analyses and outlier correction were conducted using weighted median(WM),MR-Egger regression,and MR-PRESSO.The results were expressed as odds ratios(OR)and corrected for false discovery rate(FDR).Results:MR analysis showed significant causal re-lationships between MSAB and increased risk of ADHD(OR=5.36,95％CI=2.58-7.63,PFDR=0.003),MDD(OR=1.92,95％CI=1.29-2.88,PFDR=0.003),and BD(OR=6.33,95％CI=1.56-8.73,PFDR=0.013).However,no statistically significant association was found between MSAB and ASD(OR=1.66,95％CI=0.23-5.87,PFDR=0.616).Conclusion:This study suggests a potential causal link between maternal smoking around the time of birth and an increased risk of attention deficit hyperactivity disorder,bipolar disorder,and major depressive disorder in offspring.

Objective:To investigate the causal impact of maternal smoking around birth(MSAB)on off-spring's risk of attention deficit hyperactivity disorder(ADHD),autism spectrum disorder(ASD),bipolar disorder(BD),and major depressive disorder(MDD).Methods:The datasets for MSAB and 4 psychiatric disorders were extracted from genome-wide association studies(GWAS).Mendelian randomization(MR)was employed,using in-verse variance weighting(IVW)as the primary analysis method.Sensitivity analyses and outlier correction were conducted using weighted median(WM),MR-Egger regression,and MR-PRESSO.The results were expressed as odds ratios(OR)and corrected for false discovery rate(FDR).Results:MR analysis showed significant causal re-lationships between MSAB and increased risk of ADHD(OR=5.36,95％CI=2.58-7.63,PFDR=0.003),MDD(OR=1.92,95％CI=1.29-2.88,PFDR=0.003),and BD(OR=6.33,95％CI=1.56-8.73,PFDR=0.013).However,no statistically significant association was found between MSAB and ASD(OR=1.66,95％CI=0.23-5.87,PFDR=0.616).Conclusion:This study suggests a potential causal link between maternal smoking around the time of birth and an increased risk of attention deficit hyperactivity disorder,bipolar disorder,and major depressive disorder in offspring.

Objective:To investigate the effect and influencing factors of non-invasive correction of infants with congenital auricular deformity.Methods:The data of infants with congenital auricular deformity were retrospectively analyzed, who were treated with domestic external ear orthosis in the Department of Otolaryngology Head and Neck Surgery of Tianjin Hospital from January 1, 2019 to June 30, 2023. Before treatment, the skin was prepared routinely. First, the orthosis base was installed and pressed to fit the skin around the ear. Then, according to the type of auricle deformity, the ear hook and ear cover were installed, and the adhesive tape was fixed. During the corrective treatment, the orthosis was worn all day, and the treatment was ended if there was no obvious rebound after 1 month of observation. The complications were closely observed during treatment. After the treatment, the treatment effect was evaluated and divided into markedly effective, effective and ineffective. The markedly effective rate (markedly effective ears/total ears × 100%) and effective rate [(markedly effective ears + effective ears)/ total ears × 100%] were calculated. At the same time, the cure time of the markedly effective children was recorded, and they were grouped according to different types of auricle deformities and the initial age of correction (<2, 2-6, >6 weeks groups), and the related indicators were compared. SPSS 23.0 software was used for statistical analysis. The measurement data were expressed by Mean±SD. The comparison between multiple groups was analyzed by one-way ANOVA. The pairwise comparison between groups was performed by LSD method. The counting data was expressed by frequency (% or ratio). The comparison between multiple groups was performed by χ 2 test, and the pairwise comparison between groups was performed by Fisher test with adjusted α value. Results:A total of 31 cases (55 ears) were included, including 13 males (23 ears) and 18 females (32 ears), aged 4 to 127 d. There were 13 lop ears, 6 constricted ears, 6 cup ears, 4 Stahl’s ears, 5 prominent ears, 18 helical rim deformity ears, 2 conchal crus ears and 1 Ⅱ degree microtia ear. During the treatment, 5 ears had skin lesions, 5 ears had mild allergic reactions, and 2 ears had severe allergic reactions, who improved significantly and continued treatment after removal of the external orthosis and use of erythromycin ointment. After noninvasive correction treatment, the auricle deformity of the children was improved to different extent. The overall markedly effective rate was 70.91% (39/55), and the overall effective rate was 90.91% (50/55). The markedly effective rate of lop ear, constricted ear, cup ear, Stahl’s ear, prominent ear, helical rim deformity ear, conchal ear and Ⅱ degree microtia ear were 13/13, 4/6, 4/6, 4/4, 4/5, 8/18, 2/2, 0/1 respectively. The average cure time of 39 markedly effective ears was (36.08±14.77) d. The cure time of different auricle deformity types was statistically significant ( P<0.01). Pairwise comparison between the groups showed that the cure time of lop ears was shorter than constricted ears, cup ears, Stahl’s ear, prominent ears, and that the cure time of prominent ears was longer than lop ears, constricted ears, cup ears, Stahl’s ears, helical rim deformity ears, conchal crus ears (all P<0.05). According to different initial ages of correction, the children were divided into <2-week-old group (12 cases, 21 ears), 2-6-week-old group (10 cases, 18 ears), and >6-week-old group (9 cases, 15 ears), excluding 1 Ⅱ degree microtia ear. The markedly effective rates were (90.5%) 19/21, 13/18, and 7/15, respectively, with statistically significant differences ( P<0.05). The comparison between groups showed that the markedly effective rate of <2-week-old group was significantly higher than that of >6-week-old group ( P<0.017), but there was no statistically significant difference in the cure time among the three groups ( P>0.05). Conclusion:The effect of non-invasive correction for congenital auricular deformity in infants is significant. The type of congenital auricular deformity is a key factor that affects the therapeutic effect and cure time. In lop ear, Stahl’s ear, prominent ear and conchal crus deformity, good therapeutic effects can be seen, but in constricted ear, cup ear, helical rim deformity ear and Ⅱ degree microtia, the effects are poor. The cure time of lop ear is short, while the cure time of prominent ear is long. The better effect can be acquired in the earlier non-invasive correction.

Objective:To investigate the clinical efficacy and safety of heat-clearing and spleen-invigorating method in the treatment of Helicobacter pylori (Hp) initial treatment failure population.Methods:The clinical data of 155 patients with initial Hp failure in our hospital from January 2021 to December 2022 were retrospectively analyzed. According to the treatment plan, they were divided into TCM group (66 cases) and Western medicine group (89 cases). Python 3.70 was used for bias score matching (PSM) to obtain samples with balanced covariates between groups. Finally 66 pair of cases were successfully matched according to the propensity score and the 1:1 matching principle.The TCM group was given Yiqing Capsule + Jianpi Pills (4 weeks) as a course of treatment. The Western medicine group was given four anti-Hp remedial regimen, 2 weeks for 1 course. 2 groups were treated for 1 course. Hp was detected by 14C breath test and its clearance rate was calculated. The overall symptoms of functional dyspepsia (FD) were evaluated from four aspects: postprandial fullness, early satiety, middle and upper abdominal pain, and middle and upper abdominal burning sensation. The adverse reactions during treatment were observed and the clinical efficacy was evaluated. Results:After treatment, the Hp clearance rate was 75.76% (50/66) in the TCM group and 83.33% (55/66) in the Western medicine group, which was significantly improved compared with that before treatment, without statistical significance ( χ2=1.16, P=0.281). After treatment, the scores of fullness and discomfort after meal [1 (0,2) vs. (2,4), Z=-6.85], early satiety [2 (0,2) vs. 4 (4, 6), Z=-8.02], middle and upper abdominal pain [2 (2, 4) vs. 4 (4, 6), Z=-4.48] in the TCM group were lower than those in Western medicine group ( P<0.01). The total effective rate was 75.76% (50/66) in the TCM group and 69.70% (46/66) in the Western medicine group, without statistical significance ( χ2=2.00, P=0.573). No adverse reactions occurred in the 2 groups during treatment. Conclusion:In terms of heat-clearing and spleen-invigorating method for Hp initially failed patients, its Hp clearance rate and clinical total effective rate are comparable to Western medicine, and can effectively improve the clinical symptoms of patients with Hp initial treatment failure.

Objective To observe the therapeutic effects of urolithin A(UA)on respiratory syncytial virus(RSV)-induced lung infection in neonatal mice and explore the underlying mechanisms.Methods Babl/c mice(5-7 days old)were subjected to nasal instillation of RSV and received intraperitoneal injection of saline or 2.5,5 and 10 mg/kg UA 2 h after the infection and then once daily for 2 weeks.Bronchoalveolar lavage fluid(BALF)was then collected for detection of inflammatory cells and mediators,and lung pathology was evaluated with HE staining.RSV-infected BEAS-2B cells were treated with 2.5,5 or 10 μmol/L UA.Inflammatory factors,cell viability,apoptosis and autophagy were analyzed using ELISA,CCK-8 assay,TUNEL staining,flow cytometry,Western blotting and immunofluorescence staining.The cellular expressions of miR-136 and Sirt1 mRNAs were detected using qRT-PCR.A dual-luciferase reporter system was used to verify the binding between miR-136 and Sirt1.Results In neonatal Babl/c mice,RSV infection caused obvious lung pathologies,promoted pulmonary cell apoptosis and LC3-Ⅱ/Ⅰ,Beclin-1 and miR-136 expressions,and increased the total cell number,inflammatory cells and factors in the BALF and decreased p62 and Sirt1 expressions.All these changes were alleviated dose-dependently by UA.In BEAS-2B cells,RSV infection significantly increased cell apoptosis,LC3B-positive cells and miR-136 expression and reduced Sirt1 expression(P<0.01),which were dose-dependently attenuated by UA.Dual-luciferase reporter assay confirmed the binding between miR-136 and Sirt1.In RSV-infected BEAS-2B cells with UA treatment,overexpression of miR-136 and Ex527 treatment both significantly increased the inflammatory factors and cell apoptosis but decreased LC3B expression,and these changes were further enhanced by their combined treatment.Conclusion UA ameliorates RSV-induced lung infection in neonatal mice by activating miR-136-mediated Sirt1 signaling pathway.

Objective To observe the therapeutic effects of urolithin A(UA)on respiratory syncytial virus(RSV)-induced lung infection in neonatal mice and explore the underlying mechanisms.Methods Babl/c mice(5-7 days old)were subjected to nasal instillation of RSV and received intraperitoneal injection of saline or 2.5,5 and 10 mg/kg UA 2 h after the infection and then once daily for 2 weeks.Bronchoalveolar lavage fluid(BALF)was then collected for detection of inflammatory cells and mediators,and lung pathology was evaluated with HE staining.RSV-infected BEAS-2B cells were treated with 2.5,5 or 10 μmol/L UA.Inflammatory factors,cell viability,apoptosis and autophagy were analyzed using ELISA,CCK-8 assay,TUNEL staining,flow cytometry,Western blotting and immunofluorescence staining.The cellular expressions of miR-136 and Sirt1 mRNAs were detected using qRT-PCR.A dual-luciferase reporter system was used to verify the binding between miR-136 and Sirt1.Results In neonatal Babl/c mice,RSV infection caused obvious lung pathologies,promoted pulmonary cell apoptosis and LC3-Ⅱ/Ⅰ,Beclin-1 and miR-136 expressions,and increased the total cell number,inflammatory cells and factors in the BALF and decreased p62 and Sirt1 expressions.All these changes were alleviated dose-dependently by UA.In BEAS-2B cells,RSV infection significantly increased cell apoptosis,LC3B-positive cells and miR-136 expression and reduced Sirt1 expression(P<0.01),which were dose-dependently attenuated by UA.Dual-luciferase reporter assay confirmed the binding between miR-136 and Sirt1.In RSV-infected BEAS-2B cells with UA treatment,overexpression of miR-136 and Ex527 treatment both significantly increased the inflammatory factors and cell apoptosis but decreased LC3B expression,and these changes were further enhanced by their combined treatment.Conclusion UA ameliorates RSV-induced lung infection in neonatal mice by activating miR-136-mediated Sirt1 signaling pathway.

Objective:To investigate the effect and influencing factors of non-invasive correction of infants with congenital auricular deformity.Methods:The data of infants with congenital auricular deformity were retrospectively analyzed, who were treated with domestic external ear orthosis in the Department of Otolaryngology Head and Neck Surgery of Tianjin Hospital from January 1, 2019 to June 30, 2023. Before treatment, the skin was prepared routinely. First, the orthosis base was installed and pressed to fit the skin around the ear. Then, according to the type of auricle deformity, the ear hook and ear cover were installed, and the adhesive tape was fixed. During the corrective treatment, the orthosis was worn all day, and the treatment was ended if there was no obvious rebound after 1 month of observation. The complications were closely observed during treatment. After the treatment, the treatment effect was evaluated and divided into markedly effective, effective and ineffective. The markedly effective rate (markedly effective ears/total ears × 100%) and effective rate [(markedly effective ears + effective ears)/ total ears × 100%] were calculated. At the same time, the cure time of the markedly effective children was recorded, and they were grouped according to different types of auricle deformities and the initial age of correction (<2, 2-6, >6 weeks groups), and the related indicators were compared. SPSS 23.0 software was used for statistical analysis. The measurement data were expressed by Mean±SD. The comparison between multiple groups was analyzed by one-way ANOVA. The pairwise comparison between groups was performed by LSD method. The counting data was expressed by frequency (% or ratio). The comparison between multiple groups was performed by χ 2 test, and the pairwise comparison between groups was performed by Fisher test with adjusted α value. Results:A total of 31 cases (55 ears) were included, including 13 males (23 ears) and 18 females (32 ears), aged 4 to 127 d. There were 13 lop ears, 6 constricted ears, 6 cup ears, 4 Stahl’s ears, 5 prominent ears, 18 helical rim deformity ears, 2 conchal crus ears and 1 Ⅱ degree microtia ear. During the treatment, 5 ears had skin lesions, 5 ears had mild allergic reactions, and 2 ears had severe allergic reactions, who improved significantly and continued treatment after removal of the external orthosis and use of erythromycin ointment. After noninvasive correction treatment, the auricle deformity of the children was improved to different extent. The overall markedly effective rate was 70.91% (39/55), and the overall effective rate was 90.91% (50/55). The markedly effective rate of lop ear, constricted ear, cup ear, Stahl’s ear, prominent ear, helical rim deformity ear, conchal ear and Ⅱ degree microtia ear were 13/13, 4/6, 4/6, 4/4, 4/5, 8/18, 2/2, 0/1 respectively. The average cure time of 39 markedly effective ears was (36.08±14.77) d. The cure time of different auricle deformity types was statistically significant ( P<0.01). Pairwise comparison between the groups showed that the cure time of lop ears was shorter than constricted ears, cup ears, Stahl’s ear, prominent ears, and that the cure time of prominent ears was longer than lop ears, constricted ears, cup ears, Stahl’s ears, helical rim deformity ears, conchal crus ears (all P<0.05). According to different initial ages of correction, the children were divided into <2-week-old group (12 cases, 21 ears), 2-6-week-old group (10 cases, 18 ears), and >6-week-old group (9 cases, 15 ears), excluding 1 Ⅱ degree microtia ear. The markedly effective rates were (90.5%) 19/21, 13/18, and 7/15, respectively, with statistically significant differences ( P<0.05). The comparison between groups showed that the markedly effective rate of <2-week-old group was significantly higher than that of >6-week-old group ( P<0.017), but there was no statistically significant difference in the cure time among the three groups ( P>0.05). Conclusion:The effect of non-invasive correction for congenital auricular deformity in infants is significant. The type of congenital auricular deformity is a key factor that affects the therapeutic effect and cure time. In lop ear, Stahl’s ear, prominent ear and conchal crus deformity, good therapeutic effects can be seen, but in constricted ear, cup ear, helical rim deformity ear and Ⅱ degree microtia, the effects are poor. The cure time of lop ear is short, while the cure time of prominent ear is long. The better effect can be acquired in the earlier non-invasive correction.

OBJECTIVE To predict the possible impact of pembrolizumab（PEM） as a first-line drug after being included in the national medical insurance system in the treatment of advanced or metastatic non-small cell lung cancer based on real-world data from the perspective of the national medical insurance payer， to provide a basis for the decision-making of the medical insurance department. METHODS A budget impact analysis model was constructed to compare the impact of pembrolizumab not included in medical insurance and included in medical insurance on medical insurance fund expenditure in the next five years（ 2024- 2028） with 2023 as the baseline year. The target population was the patients with EGFR gene mutation-negative and anaplastic lymphoma kinase （ALK）-negative locally advanced or metastatic non-small cell lung cancer； estimated cost mainly included the cost of drugs， the cost of adverse reaction treatment， the cost of examination， the cost of admission and monitoring， etc； equipment ratio of PEM in 183 hospitals of Guangdong province from 2020 to 2022 was used as the market share. Univariate sensitivity analysis was used to test the robustness of the basic analysis results. RESULTS When PEM was not included in the medical insurance， the medical insurance reimbursement amount of the target population from 2024 to 2028 was 4 933 623.5 thousand yuan-5 151 198.3 thousand yuan， respectively. If PEM was included in the medical insurance， the above data were 11 871 972.2 thousand yuan-14 540 571.0 thousand yuan， respectively； the increase in medical insurance reimbursement under the two scenarios was 6 720 773.9 thousand yuan-9 606 947.5 thousand yuan， respectively. The proportion of medical insurance reimbursement to the medical insurance expenditure of the year after PEM was included in medical insurance was 0.298 0%， 0.262 1%， 0.228 8%， 0.208 2%， and 0.185 7%， respectively. The increase in medical insurance reimbursement accounted for 1.084 0%， 0.995 7%， 0.888 6%， 0.886 3%， and 0.861 6% of the increase in the expenditure of the medical insurance fund in the current year， all of which showed a decreasing trend year by year. CONCLUSIONS If PEM is included in medical insurance， due to its high unit price， the medical expenditure will increase accordingly， which will have a great impact on the medical insurance fund expenditure. However， when the drug is used in patients with EGFR mutation-negative and ALK-negative locally advanced or metastatic non-small cell lung cancer， the proportion of the medical insurance reimbursement amount in the current year’s medical insurance fund expenditure and the proportion of the increase in medical insurance reimbursement in the current year’s increase in medical insurance fund expenditure are decreasing year by year.

Objective:To investigate the correlation between levels of fibroblast growth factor-23 (FGF-23) and monocyte chemoattractant protein-1 (MCP-1) and glucocorticoids-induced osteoporosis (GIOP) in children.Methods:From May. 2018 to May. 2022, 80 children with glucocorticoid osteoporosis admitted to our hospital were selected as the study subjects, and the control group was 62 children who received glucocorticoid therapy but had normal bone mass. General data were collected and bone density and bone metabolism were measured, including type 1 collagen carboxy-terminal peptide (CTX-1), type 1 procollagen amino-terminal peptide (PINP), and osteocalcin (OC). The levels of MCP-1and FGF-23 in the serum of the two groups were detected, and univariate and multivariate analysis was performed using prism software to analyze the risk factors affecting GIOP.Results:There was no significant difference in general data between the two groups (both P>0.05). The levels of FGF-23 (264.81±24.61) and MCP-1 (194.16±15.76) in serum of GIOP children were significantly higher than those in the control group (207.97±9.91; 179.00±18.34) ( t=17.13, P < 0.001; t=5.29, P < 0.001) ; Compared with those of the control group (0.88±1.08; 23.98±2.45; 8.36±3.71; 4.56±2.21), bone mineral density (0.44±0.29), PINP (16.29±3.97) and OC (6.74±3.22) levels were decreased, and CTX-1 level was increased (6.62±1.11) ( t=3.58, P<0.05; t=13.40, P<0.05; t=2.78, P<0.05; t=7.25, P<0.05) of the study group. Multivariate Logistic regression model showed that FGF-23 ( OR=1.161, 95% CI: 1.080-1.341, P<0.05), MCP-1 ( OR=1.179, 95% CI: 1.044-1.448, P<0.05) and CTX-1 ( OR=3.018, 95% CI: 1.526-10.510, P<0.05) were independent clinical risk factors for GIOP in children (all P<0.05). PINP ( OR=0.453, 95% CI: 0.169-0.740, P<0.05) was a protective factor affecting GIOP in children. Conclusion:FGF-23 and MCP-1 were independent risk factors for GIOP in children.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.