OBJECTIVE To investigate the efficacy and safety of clobazam in the additional treatment of refractory epilepsy in children， and provide reference for clinically safe and rational drug use. METHODS The literatures about additional clobazam treatment for refractory epilepsy in children were searched from PubMed， The Cochrane Library， Embase， CNKI， VIP and Wanfang database during the inception to November 2023. After literature screening and data extraction， the quality of included literature was evaluated according to quality evaluation tool for methodological evaluation indicators of non-randomized controlled trial， and then meta-analysis of single-group rate and sensitivity analysis were performed by using RevMan 5.3 software. RESULTS Finally， 18 one-arm studies were included， with a total of 1 424 children. The results showed that compared with before additional treatment， the proportion of patients with seizures-free （proportion of patients with seizure reduction of 100%） was 24%[95%CI （0.18，0.32）， P＜0.000 01] after conversion； the proportion of patients with seizure reduction ≥75% was 32%[95%CI（0.25，0.40）， P＜0.000 1] after conversion； the proportion of patients with seizure reduction ≥50% was 53%[95%CI（0.44，0.61），P＜0.000 01]； the proportion of patients with seizure reduction ＜50% or no change was 35%[95%CI（0.24，0.49），P＝0.04] after conversion； the proportion of patients with seizure increase was 9%[95%CI（0.05，0.18），P＜0.000 01] after conversion. The proportion of patients with adverse reactions was 31%[95%CI（0.23，0.40），P＜0.000 1] after conversion； the proportion of patients with discontinuation due to adverse reactions was 10%[95%CI（0.07， 0.15）， P＜0.000 01] after conversion. The common adverse drug reactions were drowsiness， fatigue and behavior change， etc. The results of the sensitivity analysis showed that the study was robust. CONCLUSIONS Clobazam is an effective additional therapy for refractory epilepsy in children， but its adverse effects should be vigilant.

Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.

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.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

ObjectiveTo investigate the mechanism of Gegen Qinliantang（GQT） on the intestinal flora of antibiotic-associated diarrhea（AAD） by 16S rRNA sequencing and network pharmacology. MethodSixty SD rats were randomly divided into six groups（n=10）， including blank group， model group， GQT high-， medium- and low-dose groups（10.08， 5.04， 2.52 g·kg^-1） as well as Lizhu Changle group（0.15 g·kg^-1）， except for the blank group， each group was given clindamycin（250 mg·kg^-1） by gavage once a day for 7 consecutive days. After successful modeling， the blank group and the model group were given equal volumes of normal saline by gavage. The other groups were given corresponding doses of drugs by gavage for 14 days. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） was used to screen the active components and targets of GQT， GeneCards， Online Mendelian Inheritance in Man（OMIM） database， Pharmacogenetics and Pharmacogenomics Knowledge Base（PharmGKB）， DrugBank and DisGeNET were used to search for AAD disease targets. The drug-disease common targets were obtained by R software. STRING was applied to analyze the target protein-protein interaction， and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis was performed. Then hematoxylin-eosin（HE） staining was used to observe the pathological changes of the colon， and 16S rRNA sequencing of AAD colon content flora structure further verified the results of network pharmacology. ResultThrough network pharmacology， it was found that 238 active components were screened from GQT and acted on 276 component targets， among which quercetin， puerarin， wogonin and apigenin were the main core components of GQT， 1 097 AAD disease targets and 127 drug-disease intersection targets. The protein-protein interaction network mainly included core targets such as protein kinase B1（Akt1）， interleukin（IL）-6 and IL-1β， which were mainly enriched in the IL-17 signaling pathway. It was verified through animal experiments that compared with the blank group， the colon structure of the model group was seriously abnormal， the intestinal epithelial columnar cells were damaged， the goblet cells were reduced， and a large number of inflammatory cells were infiltrated. Compared with the model group， the colon structure of the GQT high-dose group improved， but there were still abnormalities， the colon structure of GQT medium- and low- dose groups and Lizhu Changle group improved significantly and reached the normal level. GQT could improve the structural diversity of AAD intestinal flora. At the phylum level， the abundance of Firmicutes was increased and the abundance of Bacteroidetes was decreased. At the genus level， the abundance of Lactobacillus was increased， and the abundances of Prevotella and Bacteroides were decreased. Among them， Lactococcus could be used as a biomarker for AAD treatment with GQT， and the prediction of functional metabolism of intestinal flora revealed that GQT could promote acetate and lactate metabolic pathways in the intestine. ConclusionGQT may activate IL-17 signaling pathway by acting on the targets of Akt1 and IL-6 through key components such as quercetin and wogonin， and improve the abundance of Lactococcus in the intestinal tract as well as acetate and lactate metabolic pathways， so as to play a role in repairing the intestinal barrier for the treatment of AAD.

OBJECTIVE To investigate the efficacy and safety of different doses of zinc in the treatment of diarrhea in children， and to provide a reference for clinical safe and rational drug use. METHODS Retrieved from PubMed， Cochrane Library， Embase database， randomized controlled trials about zinc （zinc group） versus placebo or conventional treatment （control group） in the treatment of diarrhea in children were collected from the inception to October 2022. Then， the quality of the included literature was evaluated by the Cochrane Handbook 6.0， and meta-analysis and sensitivity analysis were performed by RevMan 5.3 software. RESULTS Finally， 25 RCTs were included， with a total of 8 618 children. The results of meta-analysis showed that in terms of duration of diarrhea， in zinc ＜20 mg group， the zinc group was significantly shorter than the control group [SMD＝ －0.39， 95%CI（－0.71， －0.08）， P＝0.01]， but in subgroups of ＜6 months old， there was no significant difference between the two groups [SMD＝0.01， 95%CI（－0.10， 0.11）， P＝0.88]. In zinc 20 mg group， the zinc group was significantly shorter than the control group [SMD＝－0.52， 95%CI（－0.80， －0.23）， P＝0.000 3]. In zinc ＞20 mg group， the zinc group was significantly shorter than the control group [SMD＝－0.83， 95%CI（－1.39， －0.27）， P＝0.004]. In zinc ＞10 mg （age ≤12 months） or zinc ＞ 20 mg （age ＞12 months） group （short for “constant dose group”）， the zinc group was significantly shorter than the control group [SMD＝－0.16， 95%CI（－0.27， －0.06）， P＝ 0.003]. In the aspect of diarrhea rate after 7 days of treatment，there was no significant difference in the diarrhea rate after 7 E-mail：lihuiying@etyy.cn days of treatment between the zinc group and the control group： in zinc ＜20 mg group[OR＝1.28，95%CI （0.96，1.70），P＝0.09]， in zinc 20 mg group [OR＝0.40， 95%CI （0.15，1.01），P＝ 0.05]， in constant dose group [OR＝0.64， 95%CI （0.28， 1.44）， P＝0.28]. In terms of vomiting rate， in zinc ＜20 mg group， the vomiting rate of zinc group was significantly higher than that of the control group [OR＝2.13， 95%CI （1.68， 2.70）， P＜0.001]； in constant dose group， vomiting rate of zinc group was significantly higher than that of the control group [OR＝1.84， 95%CI （1.44， 2.34）， P＜0.001]. CONCLUSIONS Zinc can significantly shorten the duration of diarrhea in children（6 months and above）， but low doses can increase the risk of vomiting， which should be taken attention in clinical.

Recent studies have showed that thrombosis is closely related to leucocytes involved in immunity. Interfering with the binding of leukocyte integrin Mac-1 and platelet GPIbα can inhibit thrombosis without affecting physiological coagulation. Mac-1-GPIbα is proposed as a potential safety target for antithrombotic agents. Guanxinning tablet (GXNT) is an oral Chinese patent medicine used for the treatment of angina pectoris, which contains phenolic acid active ingredients, such as salvianolic acids, ferulic acid, chlorogenic acid, caffeic acid, rosmarinic acid, tanshinol, and protocatechualdehyde. Our previous studies demonstrated that GXN exhibited significant antithrombotic effects, and clinical studies suggested that it did not increase bleeding risk. In addition, GXN exerted a significantly regulatory effect on immune inflammation. In the current study, we intended to evaluate the effects of GXN on bleeding events and explore the safety antithrombotic mechanism of GXN based on leukocyte-platelet interaction. First, we established a gastric ulcer model induced by acetic acid in rats and found that GXN not only did not increase the degree of gastrointestinal bleeding when gastric ulcer occurred, but also had a certain promoting effect on the healing of gastric ulcer. Second, in vitroexperiments showed that after pretreatment with GXN and activation by phorbol 12-myristate-13-acetate (PMA), the adhesion and aggregation of leukocytes with human platelets were reduced. It was also found that GXN reduced the expression and activation of Mac-1 in leucocytes, and inhibited platelet activation due to leukocyte engagement via Mac-1. Overall, the results suggest that GXN may be a safe antithrombotic agent, and its low bleeding risk mechanism is probably related to inhibited leukocyte-platelet aggregation and its interaction target Mac-1-GPIbα.
Animals ; Fibrinolytic Agents ; Humans ; Integrins ; Leukocytes ; Macrophage-1 Antigen ; Rats ; Stomach Ulcer ; Tablets ; Thrombosis

Objective:Platelet-derived growth factor alpha (PDGFRA) mutations are respectively rare in gastrointestinal stromal tumors (GIST). Most GIST with PDGFRA exon 18 mutations including D842V mutation are highly resistant to imatinib. The treatment of GIST harboring PDGFRA primary drug-resistant mutation is a major challenge. This article aims to investigate clinicopathologic features of GIST with PDGFRA-D842V mutation and the efficacy of comprehensive treatment, providing a reference for clinical practice. Methods:A retrospective cohort study was conducted to collect the clinicopathological and follow-up data of patients with GIST harboring PDGFRA mutation who were diagnosed and treated in the GIST Clinic of Renji Hospital from January 2005 to May 2020. According to the mutation site, the enrolled patients were divided into D842V mutation group and non-D842V mutation group. The differences of clinicopathologic characteristics between the two groups were compared. Furthermore, overall survival and prognostic factors were analyzed. Results:A total of 71 patients with PDGFRA-mutant GIST were included in this study, including 47 cases of D842V mutation (66.2%) and 24 cases of non-D842V mutation (33.8%). There were 28 male patients and 19 female patients in D842V mutation group, with a median age of 60 (36-82) years. There were 16 male patients and 8 female patients in non-D842V mutation group, with a median age of 62 (30-81) years. There were no significant differences in age, gender, primary location, surgical procedure, tumor size, mitotic count, expression of CD117 and DOG1, Ki-67 proliferation index and modified NIH grade between the two groups (all P>0.05). The positive rate of CD34 was 89.4% (42/47) and 62.5% (15/24) in the D842V mutation group and the non-D842V mutation group, respectively, with a statistically significant difference (χ 2=5.644, P=0.018). Among all the cases, 66 cases underwent R0 resection without preoperative treatment; two cases underwent emergency operation with R1 resection because of tumor rupture; 2 cases were not operated after the pathological and mutation types were confirmed by biopsy (one case received avapritinib treatment and obtain partial remission). One case was diagnosed as wild-type GIST per needle biopsy in another institute, and underwent R0 resection after preoperative imatinib treatment for 6 months. After surgery, 5 high-risk GIST patients with D842V mutation and 5 high-risk GIST patients with non-D842V mutation were treated with imatinib for more than one year. The median follow-up time was 37 (1-153) months. As of the last follow-up among the patients who received R0 resection, 4 patients with D842V mutation had relapse, of whom 1 was in the period of imatinib administration, and the 3-year relapse-free survival rate was 94.2%; none of the patients with non-D842V mutation had relapse. There was no statistically significant difference in relapse-free surivval between two groups ( P=0.233). Univariate analysis revealed that mitotic count ( P=0.002), Ki-67 proliferation index ( P<0.001) and modified NIH grade ( P=0.025) were the factors associated with relapse-free survival of patients with D842V mutation after R0 resection (all P<0.05). However, the above factros were not testified as independant prognostic facors in multivariate Cox analysis (all P<0.05). Conclusion:Clinicopathologic features and the efficacy of radical resection in patients with PDGFRA-D842V mutation are similar to those in patients with non-D842V mutation.

Objective:Platelet-derived growth factor alpha (PDGFRA) mutations are respectively rare in gastrointestinal stromal tumors (GIST). Most GIST with PDGFRA exon 18 mutations including D842V mutation are highly resistant to imatinib. The treatment of GIST harboring PDGFRA primary drug-resistant mutation is a major challenge. This article aims to investigate clinicopathologic features of GIST with PDGFRA-D842V mutation and the efficacy of comprehensive treatment, providing a reference for clinical practice. Methods:A retrospective cohort study was conducted to collect the clinicopathological and follow-up data of patients with GIST harboring PDGFRA mutation who were diagnosed and treated in the GIST Clinic of Renji Hospital from January 2005 to May 2020. According to the mutation site, the enrolled patients were divided into D842V mutation group and non-D842V mutation group. The differences of clinicopathologic characteristics between the two groups were compared. Furthermore, overall survival and prognostic factors were analyzed. Results:A total of 71 patients with PDGFRA-mutant GIST were included in this study, including 47 cases of D842V mutation (66.2%) and 24 cases of non-D842V mutation (33.8%). There were 28 male patients and 19 female patients in D842V mutation group, with a median age of 60 (36-82) years. There were 16 male patients and 8 female patients in non-D842V mutation group, with a median age of 62 (30-81) years. There were no significant differences in age, gender, primary location, surgical procedure, tumor size, mitotic count, expression of CD117 and DOG1, Ki-67 proliferation index and modified NIH grade between the two groups (all P>0.05). The positive rate of CD34 was 89.4% (42/47) and 62.5% (15/24) in the D842V mutation group and the non-D842V mutation group, respectively, with a statistically significant difference (χ 2=5.644, P=0.018). Among all the cases, 66 cases underwent R0 resection without preoperative treatment; two cases underwent emergency operation with R1 resection because of tumor rupture; 2 cases were not operated after the pathological and mutation types were confirmed by biopsy (one case received avapritinib treatment and obtain partial remission). One case was diagnosed as wild-type GIST per needle biopsy in another institute, and underwent R0 resection after preoperative imatinib treatment for 6 months. After surgery, 5 high-risk GIST patients with D842V mutation and 5 high-risk GIST patients with non-D842V mutation were treated with imatinib for more than one year. The median follow-up time was 37 (1-153) months. As of the last follow-up among the patients who received R0 resection, 4 patients with D842V mutation had relapse, of whom 1 was in the period of imatinib administration, and the 3-year relapse-free survival rate was 94.2%; none of the patients with non-D842V mutation had relapse. There was no statistically significant difference in relapse-free surivval between two groups ( P=0.233). Univariate analysis revealed that mitotic count ( P=0.002), Ki-67 proliferation index ( P<0.001) and modified NIH grade ( P=0.025) were the factors associated with relapse-free survival of patients with D842V mutation after R0 resection (all P<0.05). However, the above factros were not testified as independant prognostic facors in multivariate Cox analysis (all P<0.05). Conclusion:Clinicopathologic features and the efficacy of radical resection in patients with PDGFRA-D842V mutation are similar to those in patients with non-D842V mutation.

Objective: To describe the clinicopathologic features, diagnosis and differential diagnosis of ovarian carcinoid tumors. Methods: A retrospective chart review was performed of all patients diagnosed with primary ovarian carcinoid tumors at Fudan University Shanghai Cancer Centre from 2007 to 2017. Results: The histologic analysis of these carcinoid tumors revealed 3 were insular, 1 was trabecular, 1 was mucinous, and 10 were strumal. Histologic features of insular and trabecular carcinoid were similar to other parts of the neuroendocrine tumor. Strumal carcinoid was composed of thyroid tissue intimately admixed with carcinoid tumor, showing trabecular pattern. Mucinous carcinoid was resembles Krukenberg tumor. Most ovarian carcinoid tomours were diffusely positive with at least one neuroendocrine marker, especially synaptophysin (14/14) and CD56(9/10). The median follow-up time was 53 months, 1 patient with squamous-cell carcinoma of cervixrecur rence in vaginal after 37 months, and only 1 patient died of disease. The remaining patients were disease-free survival. Conclusions Primary carcinoid of the ovary is a very rare low grade malignant monodermal teratomas and somatic-type tumours arising from a dermoid. The diagnosis and differential diagnosis mainly relies on the histopathologic characteristics and the immuno-phenotype. Primary ovarian carcinoid almost always exhibit a benign clinical behavious except mucinous carcinoid.