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 investigate the clinical manifestations, treatments, and prognosis of pediatric patients with Talaromyces marneffei infection. Methods: In this retrospective study, 7 children diagnosed with Talaromyces marneffei infection in Shenzhen Children's Hospital from July 2017 to October 2021 were recruited. The clinical features, radiology, pathogen detection, immunological evaluation, treatments, and prognosis were analyzed. Results: In 7 cases, 5 were male, 2 were females. The age was from 0.75 to 8.75 years. The main clinical manifestations were fever in 7 cases, cough in 6 cases, malnutrition in 4 cases, papules in 2 cases and medical history of recurrent infection in 3 cases. Physical examination showed that all 7 patients had hepatosplenomegaly, 4 had superficial lymphadenopathy. Laboratory examination showed that 6 cases had decreased hemoglobin and 3 cases had decreased platelet. Chest CT showed that 4 cases had patchy shadows, pleural effusion, mediastinal or axillary lymph node enlargement, 3 had nodular shadows and 2 had cavities. The positive ratio of Talaromyces marneffei culture was 2/2 with tissue samples, 4/5 with bone marrow. The positive ratio was 3/4 by metagenomic next generation sequencing. The fungus was detected in 3 cases by smear microscopy of bone marrow and (or) peripheral blood. All patients were negative for human immunodeficiency virus by the immune function assay. However, 5 cases were confirmed as primary immunodeficiency disease, including 2 cases with high IgM syndrome, 2 with STAT1 gene variation, and the last with severe combined immunodeficiency (IL2RG gene variation). Exclude 1 case which gave up treatment due to acute intracranial infection, and the other patients received effective treatments along with amphotericin B, voriconazole, and itraconazole alone or in combination. Two cases relapsed after medication withdrawal, but 1 case got complete rehabilitation after hematopoietic stem cell transplantation. Conclusions: The clinical manifestations involve multisystem, the common charateristics are fever and cough. The chest CT imaging manifestations are diverse, it should be considered in differentiating tuberculosis. The amphotericin B, voriconazole and itraconazole are effective, but it will easily relapse when withdrawing those antifungal agents.
Amphotericin B/therapeutic use* ; Antifungal Agents/therapeutic use* ; Child ; Child, Preschool ; Cough ; Female ; Fever ; Humans ; Infant ; Itraconazole/therapeutic use* ; Male ; Mycoses ; Retrospective Studies ; Talaromyces ; Voriconazole

Autoimmune thyroid disease （AITD） is a complex organ-specific autoimmune disease， associated with many factors such as genetic susceptibility， environmental factors， immune system disorders， and intestinal microbiota imbalance， which seriously affect the quality of life. At present， oral medicine， iodine 131 treatment and surgical treatment are mainly adopted in clinical parctice of western medicine. Although they can exert a certain curative effect， they still have surgical risks and side effect. Modern research shows that， traditional Chinese medicine（TCM） has the characteristics of stable curative effect， multi-targeted regulation and less side effect. It has definite efficacy and unique advantages in the prevention and treatment of AITD. Helper T lymphocyte cell 17 （Th17） mediate inflammation to induce immune promotion， while regulatory T lymphocyte cell （Treg） mediate immunosuppression， Th17 and Treg cooperate to maintain the balance of the immune microenvironment. During AITD progress， Inflammatory Th17 can be high， and the levels of mediated immunosuppressive Treg are relatively decreased. The restoration of balance between the two plays a key role in the inflammatory and immune processes of AITD. In recent years， based on Th17/Treg cell axis， a large number of clinical and experimental studies on the intervention of TCM on Th17/Treg balance in AITD have been carried out in the field of TCM， and some results have been achieved. Studies have shown that intervention in the Th17/Treg signaling axis is an important mechanism for the treatment of autoimmune thyroid diseases. This paper summarizes and analyzes the previous studies on the intervention effect of Chinese medicine monomer， Chinese medicine composition and Chinese medicine compound on Th17/Treg cell axis in AITD， mainly from the aspects of intervention related inflammatory factor secretion， regulation of antibody titer and the expression of related genes of related genes. These studies will help people to understand the mechanism of TCM in interfering with the Th17/Treg balance in AITD more accurately and comprehensively， and provide references for the rational application of TCM in the prevention and treatment of autoimmune thyroid diseases in clinical practice.

There remains a significant gap in our quantitative understanding of crosstalk between apoptosis and necroptosis pathways. By employing the SWATH-MS technique, we quantified absolute amounts of up to thousands of proteins in dynamic assembling/de-assembling of TNF signaling complexes. Combining SWATH-MS-based network modeling and experimental validation, we found that when RIP1 level is below ~1000 molecules/cell (mpc), the cell solely undergoes TRADD-dependent apoptosis. When RIP1 is above ~1000 mpc, pro-caspase-8 and RIP3 are recruited to necrosome respectively with linear and nonlinear dependence on RIP1 amount, which well explains the co-occurrence of apoptosis and necroptosis and the paradoxical observations that RIP1 is required for necroptosis but its increase down-regulates necroptosis. Higher amount of RIP1 (>~46,000 mpc) suppresses apoptosis, leading to necroptosis alone. The relation between RIP1 level and occurrence of necroptosis or total cell death is biphasic. Our study provides a resource for encoding the complexity of TNF signaling and a quantitative picture how distinct dynamic interplay among proteins function as basis sets in signaling complexes, enabling RIP1 to play diverse roles in governing cell fate decisions.
Animals ; Apoptosis ; Caspase 8/metabolism* ; GTPase-Activating Proteins/metabolism* ; HEK293 Cells ; Humans ; Mice ; Mice, Knockout ; Necroptosis ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*

【Objective】 To explore the regulatory mechanism of miR-204-3p targeting EphB2 gene on proliferation, apoptosis and invasion of NSCLC. 【Methods】 A549 cells were cultured and divided into 5 groups: NC mimic group, miR-204-3p mimic group, OE NCgroup, OE EphB2 group, miR-204-3p mimic+ OE EphB2 group. MTT, flow cytometry, Transwell and scratch test were used to detect cell proliferation, cycle, apoptosis, invasion and migration. Double Luciferase Report was used to analyze the targeting relationship between mir-204-3p and EphB2. The mRNA and protein expression of miR-204-3p, EphB2 were detected by qPCR and WB. 【Results】 Innon-small lung cancer cells, the binding site of mir-204-3p and EphB2 3'UTR region, the high expression of miR-204-3p significantly inhibited the expression of EphB2 mRNA and protein(P<0.01). Compared with the Negtively control group(NC mimic group), the proliferation of A549 cells in miR-204-3p mimicgroup were significantly decrease(P<0.05), and the apototic rate was significantly increased(P<0.05). Also, the cell migration and invasion ability were also decreased significantly(P<0.05). Transfection of Ephb2 reversed the above changes. In addition, in non-small cell lung cancer tissues, miR-204-3p was negatively correlated with EphB2 expression(r=0.636, P<0.001), and the overall survival was shorter in EphB2 high expression groups than that in low expression groups(logrank χ²=3.899, P=0.049) . 【Conclusion】 MiR- 204- 3p inhibits proliferation, migration and invasion of non-small lung cancer cells and induces apoptosis by down-regulating EphB2.

Objective To discuss the application value of modified Hodge test(MHT) for screening carbapenemase-producing Enterobacteriaceae.Methods The 24 Enterobacteriaceae reduced susceptibility to carbapenems were detected by MHT.At the same time,polymerase chain reaction(PCR) was used to detect carbapenemase genes of KPC,NDM,IMP,SIM and VIM.PCR products were sequenced and the results were compared with the sequences of Gen Bank database.Comprehensive analysis the application value of MHT and PCR to detect carbapenemase.Results Among these 24 strains,13 stains appeared to produce carbapenemase by MHT,5 positive strains were found to carry carbapenemase genes by PCR.By comparing with the sequences of Gen Bank database 1 strain were confirmed to KPC-2 and 4 strains were confirmed to IMP-4.We found that 4 strains of Enterobacteriaceae,detected carbapenemase by MHT and PCR at the same time.9 strains of MHT were positive,but we couldn′t detect the carbapenemase genes.1 strain of MHT was negative,but carbapenemase gene was found in the strain.Conclusion The value of MHT to screen carbapenemase-producing Enterobacteriaceae is necessary to further study.

·AIM:To study the effects of phacoemulsification on ocular surface and corneal endothelial cells in cataract patients with diabetes mellitus.·METHODS:This study used a retrospective analysis of the clinical data to compare curative effect, the research object was 98 cases ( 98 eyes ) of cataract patients with phacoemulsification from January 2016 to December 2016 in our hospital. Patients were divided into the observation group and the control group according to whether diabetes merged. The observation group had 50 cases of cataract patients with diabetes, the control group had 48 cases of pure cataract patients. Two groups of patients underwent phacoemulsification surgery and transparent corneal incision, surgeries were completed by the same doctor, no xeroma before surgery. Preoperative glycemic control was normal for diabetic patients, no changes in eye fundus. Observation of ocular surface at postoperative 1, 3, 7d and 1mo was taken. Dry eye symptoms, lacrimal film breakup time ( BUT ) , corneal fluorescein staining ( FL ) score, SchirmerⅠtest ( SⅠt ) and corneal endothelial cell density were compared.·RESULTS: Dry eye symptom score of the two groups before and after operation had significant difference;data of the observation group at postoperative 7d and 1mo was significantly higher than that of the control group, there was statistical significance (P<0. 05), there was no significant difference at 1 and 3d after operation (P>0. 05 ). BUT of the two groups before and after surgery showed significant difference; data of the observation group at 7d and 1mo after operation was significantly lower than that of the control group, there was statistical significance ( P<0. 05 ); at 1 and 3d after operation there was no significant difference (P>0. 05). The FL score of the two groups before and after surgery had significant difference, and at 3, 7d and 1mo after operation, data of the observation group was significantly higher than that of the control group, there was statistical significance ( P< 0. 05 ); there was no significant difference at postoperative 1d (P>0. 05). The two groups' before and after surgery SⅠt had significant difference, at 1, 3, 7d and 1mo after operation, data of the observation group was significantly higher than that of the control group, there was statistical significance (P< 0. 05 ). Corneal endothelial cell density showed apparent difference of the two groups before and after surgery;at 1, 3, 7d and 1mo after operation, data of the observation group was significantly lower than that of the control group, there was statistical significance ( P<0. 05).· CONCLUSION: Phacoemulsification has significant effects on tear film break-up time, SⅠt and dry eye symptoms in patients with diabetes mellitus, which may be related to the impaired repair ability of diabetic patients.

Objective To study the effect of emodin on protein and gene expressions of the massagers in mobility signal transduction system of cholecyst smooth muscle cells in guinea pig with cholesterol calculus. Methods The guinea pigs were randomly divided into 4 groups, such as control group, gall-stone (GS) group, emodin group and ursodeoxycholic acid (UA) group. Cholesterol calculus models were induced in guinea pigs of GS, emodin and UA groups by lithogenic diet, while emodin or UA were given to the corresponding group for 7 weeks. The histomorphological and ultrastructure change of gallbladder were detected by microscope and electron microscope, the content of plasma cholecystokinin (CCK) and [Ca

Objective To study the mechanism of insulin resistance in the cholesterol gallstone formation from insulin signal transduction pathway so as to reveal the possible mechanism and the effective role of Albiflorin Granule on preventing the cholesterol gallstones. Methods Serum triglycerides (TG), free fatty acid (FFA), and total cholesterol (TC) from different groups were measured and liver cells InsR, PKB, IKK-β protein expression levels were detected by western blotting. Results Albiflorin significantly decreased the cholesterol gallstone formation rate, increased glucose infusion rate in gallstone guinea pigs and improved insulin resistance. Compared with the normal group, insulin receptor and PKB protein expression in GS group were significantly reduced. IKK-β protein in the GS group increased significantly and Albiflorin could reduce IKK-β protein expression in guinea pig liver cells. Conclusions The model of insulin resistance in cholesterol gallstone guinea pig was successfully established, which plays an important role in the cholesterol gallstone formation. All aspects of insulin signaling pathway are involved in gallstone formation. Albiflorin can regulate various aspects of insulin signal transduction pathway to prevent the formation of gallbladder.

Objective: To investigate the distribution of pathogens and drug resistance in bile and the association between the pregnane X receptor (PXR) gene polymorphisms, traditional Chinese medicine (TCM) syndromes and the risk of cholesterol gallstone disease (CGD). Methods: A total of 392 samples were enrolled in this study from January 2014 to February 2015, among which 192 patients were with CGD, and 200 samples were healthy. Strains were isolated and susceptibility testing was the disk diffusion method susceptibility testing. The patients were divided into hepatochlic hygropyrexia, stagnation of liver-qi, and the accumulation of damp. The PXR gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The association between the PXR gene polymorphisms and the risk of CGD was examined by logistic regression analysis. Results: A total of 192 cases were detected in 230 of bile culture pathogens, including Gram-negative bacteria 133 (57.83%), Gram-positive bacteria 76 (33.04%), and fungi 21 (9.13%). The top five pathogens were Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Candida albicans, and Enterococcus feces, of which 110 cases was of single infection, 48 cases of mixed infection of two strains, eight cases of mixed infection of three bacteria. Among 59 Escherichia coli, the yield extended-spectrum beta-lactamases had 40 (67.80%). The hepatochlic hygropyrexia was the most TCM syndrome, followed by stagnation of liver-qi, and the accumulation of damp was least. Different pathogens and the rs6785049 genotypes distributed differently in cholelithiasis patients with different TCM syndromes (P < 0.05). In hepatochlic hygropyrexia patients the Gram-negative bacteria was most. There was significant differences between CGD group and control group in rs6785049 (P < 0.001). Comparison with wild-type portable GG, GA genotype increased the risk of the occurrence of gallstones (OR = 0.40, 95%CI: 0.16-0.79); likewise, carrying the GA+AA genotype also increased the risk (OR = 0.38, 95%CI: 0.19-0.81). There was no significant differences in rs2276707, rs3814055 site polymorphic loci alleles in CGD group and control group. Conclusions: In the treatment of cholelithiasis, bile samples should be collected for bacterial culture and sensitivity test, and drugs should be strictly chosen based on the results. The rs6785049 polymorphisms in PXR gene may increase the risk of gallstones ontogeny, and gallstones can be early detected and prevented by detecting genotypes. rs6785049 polymorphisms in PXR gene may has relationship with TCM syndromes.