Objective:To investigate the clinical phenotype and genetic characteristics of infantile epileptic spasm syndrome caused by BRWD3 gene mutation. Methods:Clinical data of a child with BRWD3 related infantile epileptic spasm syndrome who was admitted to Department of Pediatric Neurology of Linyi People′s Hospital on August 2, 2019 were collected and followed up, whole exome sequencing technology and Sanger sequencing were applied to verify the child and his parents, and the pathogenicity of mutation site was analyzed. The studies till June 2023 were searched with keywords of " BRWD3" in both English and Chinese databases of China National Knowledge Infrastructure, Wanfang, Online Mendelian Inheritance in Man, and PubMed. The clinical phenotype and genetic characteristics of patients with BRWD3 related epilepsy were summarized. Results:The patient was a 4 years and 4 months old boy, with a clinical phenotype including severe global development delay, focal seizures (the onset age was 4 months), epileptic spasm (the onset age was 6 months), autism, megacephaly, high forehead as well as hypsarrhythmia. The whole exome sequencing results showed a de novo and frameshift variation c.4318_4319del(p.Q1441Efs*20)(NM_153252) in the BRWD3 gene, and the variation was interpreted as pathogenic (PVS1+PS2+PM2) according to the American College of Medical Genetics and Genomics variant classification criteria and guidelines. A total of 7 English literature articles were retrieved reporting 16 cases of BRWD3 gene related epilepsy in children (including 1 case of infantile epileptic spasm syndrome), and there has been no report in China yet. Totally there were 17 cases of BRWD3 gene related epilepsy including this case. All the cases showed X chromosome dominant inheritance, of whom 15 cases showed minor variations, including 7 missense variations, 3 frameshift variations, 3 splicing variations, 2 nonsense variations, and the remaining 2 cases showed large segment deletions. A total of 15 different variants were found. The phenotypes of the 17 patients mainly included epileptic seizures (17/17), intellectual disability (10/17), motor development disorder (7/17), speech impairment (9/17), megacephaly (8/17), facial malformation (8/17), autism (4/17) and hypotonia (4/17). The common seizure types were found to be focal seizures, occasionally epileptic spasm seizures and tonic seizures. Conclusions:BRWD3 gene variation related epilepsy is an X chromosome dominant genetic disease with a wide clinical phenotype spectrum. BRWD3 gene mutation c.4318_4319del(p.Q1441Efs *20) could cause infantile epileptic spasm syndrome, manifested as severe global developmental delay, epileptic spasm, focal seizures, autism, craniofacial malformation and hypsarrhythmia. This research enriches BRWD3 gene mutation spectrum.

OBJECTIVE: To identify phytochemical constituents present in the extract of flowers of Xanthoceras sorbifolia and evaluate their anti-oxidant and anti-hyperglycemic capacities. METHODS: The AlCl₃ colorimetric method and Prussian Blue assay were used to determine the contents of total flavonoids and total phenolic acids in extraction layers, and the bioactive layers was screened through anti - oxidative activity in vitro. The Waters ACQUITY UPLC system and a Waters ACQUITY UPLC BEH C₁₈ column (2.0 mm × 150 mm, 5 μm) were used to identify the ingredients. And anti-oxidative ingredients were screened by off-line UPLC-QTOF-MS/MS-free radical scavenging. The ameliorative role of it was further evaluated in a high-fat, streptozotocin-induced type 2 diabetic rat model and the study was carried out on NADPH oxidase (PDB ID: 2CDU) by molecular docking. RESULTS: Combined with the results of activity screening in vitro, the anti - oxidative part was identified as the ethyl acetate layer. A total of 24 chemical constituents were identified by liquid chromatography-mass spectrometry in the ethyl acetate layer and 13 main anti-oxidative active constituents were preliminarily screened out through off-line UPLC-QTOF-MS/MS-free radical scavenging. In vivo experiments showed that flowers of X. sorbifolia could significantly reduce the blood glucose level of diabetic mice and alleviate liver cell damage. Based on the results of docking analysis related to the identified phytocompounds and oxidase which involved in type 2 diabetes, quercetin 3-O-rutinoside, kaempferol-3-O-rhamnoside, isorhamnetin-3-O-glucoside, and isoquercitrin showed a better inhibitory profile. CONCLUSION The ethyl acetate layer was rich in flavonoids and phenolic acids and had significant anti-oxidant activity, which could prevent hyperglycemia. This observed activity profile suggested X. sorbifolia flowers as a promising new source of tea to develop alternative natural anti-diabetic products with a high safety margin.

OBJECTIVE To compare efficacy and safety of continuous pump versus intermittent infusion of amphotericin B in the treatment of invasive fungal infection， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from PubMed， the Cochrane Library， Web of Science， Embase， Wanfang， CNKI， CBM and VIP database， randomized controlled trial （RCT） and cohort study about 24 h continuous pump （trial group） versus intermittent infusion （control group） of amphotericin B were collected from the inception to Jan. 2023. After literature screening and data extraction， the quality of RCT was evaluated with modified Jadad scale， and the quality of cohort study was evaluated with Newcastle-Ottawa scale. Meta-analysis and sensitivity analysis were performed by using RevMan 5.4 software. RESULTS A total of 7 literature were included， involving 1 RCT and 6 cohort studies with a total of 767 patients. The results of meta-analysis showed that the clinical effective rate [RR＝1.44， 95%CI （1.13，1.83）， P＝0.003] of trial group was significantly higher than that of control group， and all-cause mortality rate [RR＝0.37， 95%CI（0.19，0.72），P＝0.003] and the incidence rate of infusion reaction [RR＝0.28，95%CI（0.18，0.43）， P＜0.000 01] were significantly lower than control group； there was no statistical significance in the incidence rate of renal impairment between 2 groups [RR＝0.71，95%CI（0.45，1.11），P＝0.13] . The sensitivity analysis results showed that the results obtained in this study were robust. CONCLUSIONS The efficacy and safety of 24 h continuous pump of amphotericin B are better than those of intermittent infusion in the treatment of invasive fungal infection.

BACKGROUND: Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear. METHODS: We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted. RESULTS: Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways. CONCLUSIONS GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Sorafenib/therapeutic use* ; Liver Neoplasms/metabolism* ; Glutamate-Ammonia Ligase/metabolism* ; Hepatectomy ; Retrospective Studies ; Prognosis ; Neoplasm Recurrence, Local/surgery*

Objective:To investigate the Correlation between ADC combined with serum C-reactive protein (CRP) and delayed encephalopathy after carbon monoxide poisoning (DEACMP), It provides scientific basis for early prediction of DEACMP.Methods:According to the design principle of case-control study, the data of acute carbon monoxide poisoning (ACOP) patients admitted to Shandong Provincial Hospital from December 2017 to December 2021 were retrospectively selected. Among them, patients with DEACMP were selected as the case group, without DEACMP were used as the control group. Univariate and multivariate analyses were performed on the two groups. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of ADC combined with CRP as a combined predictor for disease.Results:A total of 89 patients with ACOP were included, including 33 patients with DEACMP and 56 patients without DEACMP. There were no significant differences in gender, age, smoking, drinking, and underlying diseases (hypertension, coronary heart disease) between groups ( P>0.05). Logistic regression analysis showed that white blood cell count (WBC) ( OR=1.64, 95% CI: 1.19-2.26, P=0.003), CRP ( OR=1.22, 95% CI: 1.03-1.45, P=0.019) and ADC value of central semiovale white matter ( OR=0.99, 95% CI: 0.98-1.00, P=0.010) were associated with DEACMP in patients with ACOP. The ROC curve results showed that the area under the ROC of ADC combined with CRP in the center of semiovale was 0.765 (95% CI: 0.656-0.845), the specificity was 87.9%, the sensitivity was 23.2%, and the cut-off value was 3.5°. Conclusions:WBC, CRP and ADC value of central semiovale are independent factors for DEACMP. ADC value of central semiovale combined with CRP has more clinical value in the early diagnosis of DEACMP. For ACOP patients with DEACMP triggering factors, the diagnosis and treatment awareness of early screening of brain magnetic resonance imaging should be strengthened to avoid DEACMP.

Objective:To explore the differences of fecal calprotectin (FC), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) between colon and small intestinal Crohn′s disease, and their predictive values for disease activity and mucosal healing in patients with small intestinal Crohn′s disease.Methods:From January 2017 to January 2023, 64 patients with Crohn′s disease who underwent capsule endoscopy in the First Affiliated Hospital of Zhejiang Chinese Medical University were enrolled, among them 28 patients had only small intestinal lesions (small intestine group) and 36 patients had lesions involving both small intestine and colon or only colon involvement (ileocolon group). The FC, CRP, and ESR levels of the two groups were detected and compared 15 days before capsule endoscopy examination. Wilcoxon rank-sum test was used for statistical analysis. Receiver operating characteristic curve analysis was used to evaluate the predictive value of FC, CRP, and ESR for disease activity and mucosal healing in patients with small intestinal Crohn′s disease.Results:The FC, CRP, and ESR levels of the small intestine group during the active phase of the disease were 1 689.00 μg/g (727.75 μg/g, 1 800.00 μg/g), 5.67 mg/L (1.00 mg/L, 17.01 mg/L), and 4.50 mm/1 h (2.00 mm/1 h, 11.00 mm/1 h), respectively; while FC, CRP, and ESR levels during the mucosal healing phase were 112.00 μg/g (46.50 μg/g, 130.50 μg/g), 1.00 mg/L (1.00 mg/L, 1.62 mg/L), and 2.00 mm/1 h (2.00 mm/1 h, 5.50 mm/1 h), respectively. The FC, CRP, and ESR levels of the ileocolon group during the active phase of the disease were 1 800.00 μg/g (895.50 μg/g, 1 800.00 μg/g), 4.94 mg/L (3.10 mg/L, 14.80 mg/L), and 10.00 mm/1 h (2.00 mm/1 h, 27.75 mm/1 h), respectively, while FC, CRP, and ESR levels during the mucosal healing phase were 66.00 μg/g (32.50 μg/g, 97.50 μg/g), 1.00 mg/L (1.00 mg/L, 1.55 mg/L), and 2.00 mm/1 h (2.00 mm/1 h, 4.50 mm/1 h), respectively. There were no statistically significant differences in FC, CRP, and ESR between the small intestine group and the ileocolon group during the active phase of the disease and mucosal healing phase (all P> 0.05). In the small intestine group, the levels of FC and CRP of patients during the active phase of the disease were 1 173.00 μg/g (312.00 μg/g, 1 800.00 μg/g) and 2.10 mg/1 L (1.00 mg/L, 16.00 mg/L), which were both higher than those of patients during the mucosal healing phase (112.00 μg/g (46.50 μg/g, 130.50 μg/g) and 1.00 mg/L (1.00 mg/L, 1.62 mg/L)), and the differences were statistically significant ( Z=-4.35 and-2.67, P<0.001 and =0.008). In the small intestine group, the level of ESR of patients during the active phase of the disease was 4.00 mm/1 h (2.00 mm/1 h, 16.00 mm/1 h), and there was no significant difference compared with that of patients during the mucosal healing phase (2.00 mm/1 h (2.00 mm/1 h, 5.50 mm/1 h)) ( P>0.05). When the cut-off level of FC was 188.50 μg/g, the sensitivity, specificity, and area under the curve for predicting disease activity in patients with small intestinal Crohn′s disease was 93.3%, 100.0%, and 0.964, respectively. When the cut-off value of CRP was 3.12 mg/L, the sensitivity, specificity, and area under the curve for predicting disease activity in patients with small intestinal Crohn′s disease was 46.7%, 92.3%, and 0.744, respectively. When the cut-off level of ESR was 10.00 mm/1 h, the sensitivity, specificity, and area under the curve for predicting disease activity in patients with small intestinal Crohn′s disease was 33.3%, 100.0%, and 0.654, respectively. There were no statistically significant differences in the area under the curve between the combinations of FC and CRP, FC and ESR, FC, CRP and ESR, and FC alone for predicting disease activity in patients with small intestinal Crohn′s disease (0.964, 0.959, and 0.959 vs. 0.964, all P> 0.05). There was a statistically significant difference in the area under the curve between the combination of CRP and ESR and FC alone in predicting disease activity in patients with small intestinal Crohn′s disease (0.708 vs. 0.964, Z=-2.57, P=0.010). Conclusions:There are no statistically significant differences in FC, CRP, and ESR between colon and small intestinal Crohn′s disease. FC has a high predictive value for disease activity and mucosal healing in patients with small intestinal Crohn′s disease and has certain clinical application value.

OBJECTIVE To systematically evaluate the adverse effects of drug-resistant tuberculosis （DR-TB） drugs on pregnant women and fetuses ，so as to provide evidence-based reference for clinical medication. METHODS PubMed，Cochrane Library，Embase，CBM，CNKI，Wanfang database and VIP were searched by computer to collect randomized controlled trials （RCTs），cohort studies ，case-control studies ，case series and case reports about pregnant women exposed to DR-TB drugs. The retrieval time limit was from the establishment of each database to August 20，2021. After selecting the literature and extracting the data，the bias risk assessment tool recommended by 6.2 version of Cochrane system evaluator manual was used to evaluate the quality of the included RCTs ；Newcastle-Ottawa scale was used to evaluate the quality of the included cohort studies and case-control studies ；IHE scale issued by the Canadian Institute of Health Economics （IHE）was used to evaluate the quality of the included case series and case reports. RevMan 5.1 software was used for Meta-analysis of non-comparative binary data. RESULTS A total of 13 literature were included ，including 7 case series and 6 case reports ，involving 203 patients and 204 newborns；among them，there were 6 literature about non-comparative binary data. The results of meta-analysis showed that after exposure to DR-TB drugs，no newborn had birth defects ；the mortality of pregnant women was 0.09[95％CI（0.06，0.15），P＜0.000 01]；the neonatal mortality was 0.02[95％CI（0，0.06），P＜0.000 01]；the incidence of preterm birth was 0.14[95％CI（0.03，0.43），P＝0.02]；the incidence of infants with low birth weight was 0.17[95％CI（0.04，0.51），P＝0.06]；the incidence of growth retardation was 0.15[95％CI（0.09，0.22），P＜0.000 01]；the incidence of stillbirth was 0.05[95％CI（0.02，0.09），P＜0.000 01]；the incidence of abortion was 0.08[95％CI（0.05，0.14），P＜0.000 01]. CONCLUSIONS Pregnant women exposed to DR-TB drugs can cause pregnant women ’s death and abortion ，neonatal death ，premature birth ，infants with low birth weight ，growth retardation and stillbirth，but there is no neonatal birth defect ；these adverse outcomes may be related to the history of DR-TB.

Background::Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL.Methods::This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+.Results::A total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups (P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups ( P= 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%; P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%; P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%; P= 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%; P= 0.041), respectively, in the HID and MSD groups. Conclusion::HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph- high-risk B-ALL patients.Trial registration::ClinicalTrials.gov: NCT01883180, NCT02673008.

Objective:To evaluate the impact of the reform of the county medical community on the expenditure of medical insurance funds, and to provide references for maintaining the stability of the medical insurance fund and deepening the reform of the medical community.Methods:Medical insurance data of urban and rural residents in M County, Yunnan province from 2016 to 2019 were collected, and a discontinuous time series model was used to analyze the impact of county medical community reform on medical insurance fund expenditures.Results:Since the reform, the number of patients discharged from county-level hospitals has shown a downward trend, averaging a decrease of 25.996 people per month; yet increases have emerged with the average hospitalization expenditure, the average hospitalization overall fund expenditure, and the average outpatient overall fund expenditure, averaging a monthly increase of 90.931 yuan, 50.014 yuan and 1.528 yuan respectively. The average hospitalization expenditure, the average hospitalization overall fund expenditure, and the average outpatient overall fund expenditure of the township hospitals all showed an upward trend, averaging a monthly increase of 31.191 yuan, 38.678 yuan and 0.085 yuan respectively. The flow of external medical insurance funds of the medical community has shown a continuous upward trend, averaging a monthly increase of hospitalization fund expenditures of 33.005 yuan, and a monthly increase of outpatient overall fund expenditures of 4.896 yuan overall.Conclusions:The M County medical community should further strengthen the top-level design, explore the reform of medical insurance payment methods, improve the regional information platform, standardize the referral system, and strengthen supervision to deepen the construction of the medical community to ensure the sustainable operation of medical insurance funds.

Objective:To investigate the efficacy of oseltamivir combined with LianhuaQingwen granule in the treatment of influenza. Methods:Ninety-two patients with influenza who received treatment in Wenzhou People's Hospital from October 2017 to October 2019 were included in this study. They were randomly assigned to receive treatment with Lianhua Qingwen granules (control group, n = 46) or Lianhua Qingwen granules combined with oseltamivir (study group, n = 46) for 5 d. After treatment, clinical efficacy and symptom disappearance time (fever disappearance time, cough disappearance time, sore throat disappearance time) were compared between the control and study groups. Changes in immune function [C-reactive protein, interleukin-6, T lymphocyte subsets (CD 4+/CD 8+)] after treatment relative to before treatment, and the incidence of adverse reactions were compared between the two groups. Results:After treatment, total effective rate in the study group was significantly higher than that in the control group [97.83% (45/46) vs. 71.74% (33/46), χ 2 = 12.132, P < 0.001]. Fever disappearance time, cough disappearance time, sore throat disappearance time in the study group were significantly shorter than those in the control group [(2.04 ± 0.51) d vs. (3.15 ± 1.22) d, (3.25 ± 1.10) d vs. (4.53 ± 1.36) d, (2.72 ± 0.84) d vs. (3.95 ± 1.02) d, t = 5.693, 4.963, 6.313, all P < 0.001]. After treatment, C-reactive protein and interleukin-6 levels in the study and control groups were significantly decreased compared with before treatment [(9.24 ± 2.51) mg/L vs. (3.32 ± 2.21) mg/L, (9.21 ± 2.46) mg/L vs. (5.52 ± 2.10) mg/L, (70.25 ± 25.10) mg/L vs. (47.57 ± 14.50) mg/L, (69.24 ± 25.43) mg/L vs. (55.23 ± 16.44) mg/L]. After treatment, C-reactive protein and interleukin-6 levels in the study group were significantly lower than those in the control group ( t = 5.307, 3.138, all P < 0.001). After treatment, the number of CD 4+/CD 8+ cells in the study and control groups was significantly increased compared with before treatment [(0.45 ± 0.21) vs. (1.77 ± 0.59), (0.46 ± 0.18) vs. (1.08 ± 0.42)]. After treatment, the number of CD 4+/CD 8+ cells in the study group was significantly higher than that in the control group ( t = 14.295, 9.202, both P < 0.001). There were no significant differences in the incidence of nausea, vomiting, rash and diarrhea between the two groups within 5 d of treatment (all P > 0.05). Conclusion:Oseltamivir combined with Lianhua Qingwen granules exhibits better therapeutic effect than Lianhua Qingwen granules alone. It can strengthen immune function and shorten the durations of fever, cough and sore throat in patients with influenza.