ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

Objective: To explore the laboratory testing methods and clinical management strategies for immune hemolytic anemia induced by Ceftizoxime sodium drug-dependent antibodies. Methods: Patient blood samples were subjected to blood typing, direct antiglobulin test, and unexpected antibody identification. Ceftizoxime sodium drug-dependent antibodies were detected using the immune complex method and drug-sensitized red cell method. The properties and titers of the drug antibodies were further assessed. Flow cytometry was used to assess the complement activation capacity of the drug antibodies in vitro. Results: Direct antiglobulin tests (IgG and C3d) were positive. Ceftizoxime sodium drug-dependent antibodies were identified using both the immune complex method and the sensitized red cell method, their titers significantly increased following the addition of the drug. Flow cytometry confirmed the complement activation capability of these antibodies and identified 30 minutes as the optimal time for activation in vitro. The patient's condition improved rapidly after drug withdrawal and supportive transfusion, resulting in a favorable outcome. Conclusion: Ceftizoxime sodium can cause drug-induced immune hemolytic anemia via complement activation mediated by drug-dependent antibodies. Serological testing is essential for diagnosing drug-induced hemolytic anemia. Clinicians should be vigilant for this adverse reaction. The offending drug must be promptly discontinued, and supportive care should be initiated upon the onset of symptoms.

Objective To explore the effect of ritodrine hydrochloride combined with magnesium sulfate in the treatment of threatened abortion in older patients with a second child and to analyze its possible mechanism of action.Methods From March 2020 to December 2021,100 older second-child patients with threatened abortion at Handan Maternal and Child Health Hospital were selected and divided into control and observation groups using a random number table method,with 50 cases in each group.The control group was treated with magnesium sulfate based on general intervention measures(bed rest,intermittent oxygen inhalation,nutrition intake,and psychological nursing),while the observation group was treated with ritodrine hydrochloride combined with magnesium sulfate based on general inter-vention measures.The treatment effects,immunoregulatory function indicators[serum blocking antibody(BA)and anticardiolipin antibody(ACA)],sex hormone levels[progesterone(P),estradiol(E2),β-human chorionic gonadotropin(β-hCG)]and related cytokines[pregnan-cy-associated plasma protein A(PAPP-A),human leukocyte antigen G(HLA-G),and interleukin-10(IL-10)]before and after treatment,as well as maternal and infant outcomes and adverse reactions were compared.Results The total efficacy rate was higher in the observa-tion group than in the control group(96％vs.80％,P＜0.05).Compared with before treatment,the serum BA-positivity rate significantly increased and the ACA-positivity rate significantly decreased in both groups after treatment(both P＜0.05).However,after treatment the serum BA-positivity rate was higher in the observation group than in the control group,and the ACA-positivity rate was lower than that in the control group(both P＜0.05).Compared with before treatment,the serum P,E2,β-hCG,PAPP-A,HLA-G,and IL-10 levels signifi-cantly increased at the end of treatment and 2 weeks after treatment in both groups.The levels of sex hormones and related cytokines in the observation group were higher than those in the control group at the end of treatment and two weeks after treatment(both P＜0.05).The success rates of pregnancy maintenance,full-term delivery,and natural labor were higher in the observation group than in the control group;however,the incidences of abortion,premature delivery,cesarean section,and adverse neonatal outcomes were lower than those in the control group(all P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＜0.05).Conclusion The combination of ritodrine hydrochloride and magnesium sulfate has significant therapeutic effects in the treatment of threatened abortion in older women with a second pregnancy.It can improve maternal immune regulation,regulate sex hormone levels and PAPP-A,HLA-G,and IL-10 levels,reduce adverse maternal and fetal outcomes,and does not increase adverse reactions.

Objective:To explore the effects of the immune responses mediated by topological structures of three-dimensional bioprinted scaffolds on hair follicle cycle in mice.Methods:The study was an experimental research. The alginate-gelatin composite hydrogels were printed into scaffolds using a three-dimensional bioprinter and named T45 scaffolds, T60 scaffolds, and T90 scaffolds according to the 3 topological structures of the scaffolds (the rotation angles of the printhead during printing were 45°, 60°, and 90°, respectively), and the morphology of the three scaffolds was observed after cross-linking by naked eyes. Nine 8-week-old female C57BL/6J mice were divided into T45 group, T60 group, and T90 group, according to the random number table, with three mice in each group, and the T45, T60, and T90 scaffolds were subcutaneously implanted on the back of mice, respectively. On post implantation day (PID) 7, the hair growth in the dorsal depilated area of mice was observed, the thickness of the fiber capsule around the scaffolds was observed by hematoxylin-eosin staining, and the expression levels of CD68, bone morphogenetic protein-2 (BMP-2), and tumor necrosis factor (TNF) protein in the tissue surrounding the scaffolds were observed by immunofluorescence staining. The samples of the above experiments were all 3.Results:The topological structures of the three scaffolds were all clear with high fidelity after cross-linking. On PID 7, the hair growth was obvious in the dorsal depilated area of mice in T45 group and T90 group, while hair growth was slow in the scaffold implantation area of mice in T60 group, which was significantly different from that of the unimplanted area. On PID 7, compared with (18±4) μm in T90 group, the thickness of both the fiber capsule around the scaffolds ((39±4) and (55±8) μm) of mice in T45 group and T60 group was significantly increased ( P<0.05); the thickness of the fiber capsule around the scaffolds of mice in T60 group was also significantly increased compared with that in T45 group ( P<0.05). On PID 7, the expression level of CD68 protein in the tissue surrounding the scaffolds of mice in T60 group was significantly higher than the levels in T45 group and T90 group (with both P values <0.05). The expression level of BMP-2 protein in the tissue surrounding the scaffolds of mice in T60 group was significantly higher than the levels in T45 group and T90 group (with both P values <0.05), and the expression level of BMP-2 protein in the tissue surrounding the scaffolds of mice in T45 group was significantly higher than that in T90 group ( P<0.05). The expression level of TNF protein in the tissue surrounding the scaffolds of mice in T60 group was significantly lower than the levels in T45 group and T90 group (with both P values <0.05). Conclusions:Three-dimensional bioprinted scaffolds with different topological structures mediate different degrees of immune responses after being implanted in mice. A moderate immune response promotes hair growth in depilated area of mice, while an excessive immune response results inhibits the hair follicle entering into the anagen phase.

Objective To investigate the factors influencing prognosis in patients with acute myocardial infarction complicated with cardiogenic shock undergoing primary percutaneous coronary intervention(PPCI).Methods Patients with acute myocardial infarction complicated with cardiogenic shock who underwent PPCI at our hospital between January 2015 and December 2019 were enrolled.Clinical baseline characteristics,coronary angiography and PCI-related parameters,and mechanical support information were collected.The patients were followed up for one year and divided into survival and death groups based on their survival status within one year.Differences in various factors between the two groups were compared.Results A total of 40 patients were enrolled,including 26 in the survival group and 14 in the death group.There were no differences in baseline data,diagnosis,risk factors,and comorbidities between the two groups.The survival group had a lower heart rate and higher blood pressure trend at admission compared to the death group.Myocardial enzymes were significantly lower in the survival group compared to the death group(median CK peak:496.00(198.25,2 830.00)U/L vs.3 040.00(405.75,5 626.53)U/L,P=0.003;median CK-MB peak:52.65(31.75,219.50)U/L vs.306.00(27.25,489.63)U/L,P=0.006).When comparing coronary angiography and PCI-related indicators between the two groups,the survival group had a higher rate of complete revascularization compared to the control group(53.85％vs.21.43％,P=0.048).The survival group had a higher proportion of extracorporeal membrane oxygenation(ECMO)combined with intra-aortic balloon pump(IABP)support compared to the control group[38.46％vs.7.14％,P=0.034].Conclusions Survival in patients with acute myocardial infarction complicated with cardiogenic shock undergoing PPCI is associated with lower level of myocardial enzymes,ECMO combined with IABP support and complete revascularization.

Identifying the compound formulae-related xenobiotics in bio-samples is full of challenges.Conventional strategies always exhibit the insufficiencies in overall coverage,analytical efficiency,and degree of automation,and the results highly rely on the personal knowledge and experience.The goal of this work was to establish a software-aided approach,by integrating ultra-high performance liquid chromatography/ion-mobility quadrupole time-of-flight mass spectrometry(UHPLC/IM-QTOF-MS)and in-house high-definition MS2 library,to enhance the identification of prototypes and metabolites of the compound formulae in vivo,taking Sishen formula(SSF)as a template.Seven different MS2 acquisition methods were compared,which demonstrated the potency of a hybrid scan approach(namely high-definition data-independent/data-dependent acquisition(HDDIDDA))in the identification precision,MS1 coverage,and MS2 spectra quality.The HDDIDDA data for 55 reference compounds,four component drugs,and SSF,together with the rat bio-samples(e.g.,plasma,urine,feces,liver,and kidney),were acquired.Based on the UNIFI? platform(Waters),the efficient data processing workflows were estab-lished by combining mass defect filtering(MDF)-induced classification,diagnostic product ions(DPIs),and neutral loss filtering(NLF)-dominated structural confirmation.The high-definition MS2 spectral li-braries,dubbed in vitro-SSF and in vivo-SSF,were elaborated,enabling the efficient and automatic identification of SSF-associated xenobiotics in diverse rat bio-samples.Consequently,118 prototypes and 206 metabolites of SSF were identified,with the identification rate reaching 80.51％and 79.61％,respectively.The metabolic pathways mainly involved the oxidation,reduction,hydrolysis,sulfation,methylation,demethylation,acetylation,glucuronidation,and the combined reactions.Conclusively,the proposed strategy can drive the identification of compound formulae-related xenobiotics in vivo in an intelligent manner.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To explore the clinical application effect of the nursing model of the doctor-nurse collaborative responsibility system in preventing catheter-related infection with tunnel-cuffed catheter(TCC).Methods A total of 130 hemodialysis patients using TCC were enrolled from the department of nephrology of Tianjin Hospital,Tianjin University,during the period from January 2021 to December 2021 were selected as research objects.They were divided into two groups based on different admission times,with 65 patients in each group.The control group,comprising patients admitted from January 2021 to June 2021,received traditional nursing care;while the study group,consisting of patients admitted from July 2021 to December 2021,followed a doctor-nurse collaborative responsibility nursing model.Incidence of catheter-related infection,the length of hospital stay,the duration of catheter placement and patients'satisfaction with nursing were calculated,and the results were compared between the two groups.Results Compared with the control group,the incidence of catheter exit-site infection,incidence of TCC,incidence of total infection were all significantly decreased in the study group[the incidence of catheter exit-site infection:3.08%(2/65)vs.15.38%(10/65),incidence of TCC:1.54%(1/65)vs.6.15%(4/65),incidence of total infection:6.15%(4/65)vs.24.62%(16/65),all P<0.05].There was no significant difference in incidence of catheter-related bloodstream infection between the observation group and the control group[1.54%(1/65)vs.3.08%(2/65),P>0.05].Compared with the control group,the length of hospital stay in the observation group was significantly shortened in the study group(days:12.45±3.62 vs.19.25±5.09,P<0.05),the duration of catheter placement was increased remarkably in the study group(days:83.64±14.20 vs.65.27±12.38,P<0.05),and the patients'satisfaction with nursing was significantly improved in the study group[96.92%(63/65)vs.81.54%(53/65),P<0.05].Conclusion The implementation of the nursing model of doctor-nurse collaborative responsibility system can effectively reduce the occurrence of catheter-related infection with TCC,dramatically decrease hospitalization time and significantly improve the patients'satisfaction with nursing.

Objective:To evaluate the clinical value of CD4 + T lymphocyte subsets such as helper Th2 in patients with recurrent uveitis (BU) in Beh?et′s disease (BD). Methods:The clinical data of 153 hospitalized patients diagnosed with Beh?et′s disease from January 1, 2020 to June 30, 2023 in the Second Hospital of Shanxi Medical University were retrospectively analyzed. The subsets of CD4 + T lymphocytes were measured, including helper T cells (Th cells) such as Th1, Th2, Th17 and regulatory T cells (Treg cells), biochemical lipid indexes (TC, TG, etc.), the frequency of oral ulcers in the past 1 year, the frequency of genital ulcers in the past 1 year, and drug use before admission;According to whether there was ocular involvement and uveitis, 153 cases of BD were divided into Beh?et non-uveitis group (non-BU group) and Beh?et uveitis group (BU group). The above indexes and independent correlation factors of recurrent BU were compared between BU group and non-BU group;The above indexes and independent correlation factors of recurrent BU were compared between BU group and non-BU group. The levels of cytokines and ICBD total score, the correlation between ICBD total score and various cytokines, and the diagnostic performance of Th2 cells were compared between BU group and non-BU group.The statistical methods were Mann-Whitney U test, independent sample t test, Chi-square test, multiple logistic regression analysis, Pearson correlation analysis and receiver operating characteristic curve (ROC) analysis. Results:①The levels of Th1, Th2, Th17 cells, TC and TG in BU group were higher than those in non-BU group [133.87 (93.38, 229.87)/μl vs. 102.51(64.25, 149.23)/μl] and [9.43 (5.84, 14.13)/μl vs. 6.78(4.23, 9.44)/μl], [15.53 (9.36, 25.27)/μl vs. 9.83(5.46, 14.76)/μl], [4.21 (3.89, 4.90) mmol/L vs. 3.89(3.37, 4.34)mmol/L)], [1.43(1.00, 2.21)mmol/L vs. 0.96(0.69, 1.38)mmol/L], The differences were statistically significant ( Z=-3.24, Z=-3.05, Z=-3.94, Z=-2.25, Z=-3.47; all P<0.05); There was no statistical significance in Chi-square test between the two groups ( χ2=5.69, P>0.05).②The levels of IL-2, IL-10 and total ICBD score in BU group were higher than those in non-BU group, with statistical significance ( Z=-2.12, Z=-2.29, t=-6.48; all P<0.05). ③ The results of multiple logistic regression analysis showed that Th2 was an independent correlation factor for BU [ OR value (95% CI) was 1.143(1.007, 1.298), P=0.039]. The total score of BU patients was correlated with Th2 and Th17 cells. ROC analysis showed that the sensitivity of Th2 in diagnosing BU was 68.8%, the specificity was 49.5% and the area under the curve (95% CI) was 0.697 (0.585, 0.809) (P=0.001). Conclusion:CD4 + T lymphocyte subsets such as the absolute number of Th2 cells are related to BU, which is an important indicator to observe the severity of disease progression in BU patients, and has certain clinical value in evaluating the recurrence of BU in BD patients.

Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.