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 analyze the changes of B lymphocyte(B cells)subsets in peripheral blood of patients with chronic hepatitis B(CHB)and to explore its clinical significance.Methods Peripheral blood samples were collected from 37 treatment-na?ve CHB patients who were admitted to the Fifth Medical Center of PLA General Hospital from July 2022 to October 2022,and peripheral blood samples collected from 18 healthy individuals who have received the hepatitis B vaccine as healthy controls(HC).The study subjects'clinical indexes such as age,HBV DNA viral load,HBsAg quantification,HBeAg semi quantification,ALT,AST,and AST/ALT ratio were collected.The change characteristics of the frequency,phenotypic and functional markers of peripheral blood B lymphocytes and their subsets were compared between CHB and HC.Using multi-color flow cytometry,and the correlation between them and clinical indexes was analyzed.Results Frequency analysis of each subset of B cells showed that compared with HC,the frequency of total B cells,transitional B cells and naive B cells was decreased(P<0.05),while the frequency of mature B cells,memory B cells,atypical memory B cells and activated memory B cells was increased in CHB patients(P<0.01).And there was no significant difference in the frequency of resting memory B cells between the two groups(P>0.05).The results of functional analysis showed that compared with HC,the expression levels of CD79b on total B cells,mature B cells,memory B cells,naive B cells,activated memory B cells,atypical memory B cells and resting memory B cells in CHB patients were increased(P<0.05).The expression level of programmed cell death protein-1(PD-1)on atypical memory B cells in CHB patients was also higher than that in HC group(P<0.05).The results of correlation analysis showed that the frequency of total B cells in CHB patients was slightly negatively correlated with age(r=-0.39,P<0.05),while the expression of programmed death-1(PD-1)on total B cells,mature B cells,transitional B cells,memory B cells and naive B cells were slightly positively correlated with age(r>0.36,P<0.05).Conclusions Chronic HBV infection leads to depletion of the frequency and function of a portion of B cells in the peripheral blood of CHB patients,and age is a potential risk factor for the decline in humoral immune function in CHB patients.

Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults.The high levels of glucose trigger multiple intracellular oxidative stress pathways,such as POLDIP2,resulting in excessive reactive oxygen species(ROS)pro-duction and increased expression of vascular cell adhesion molecule-1(VCAM-1),hypoxia-inducible factor 1α(HIF-1α),and vascular endothelial growth factor(VEGF),causing microvascular dysfunction.Dihydromyricetin(DMY)is a natural flavonoid small molecule antioxidant.However,it exhibits poor solubility in physiological environments,has a short half-life in vivo,and has low oral bioavailability.In this study,we present,for the first time,the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles(Fe-DMY NCPs),formed by combining DMY with low-toxicity iron ions.In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endo-thelial cells by high glucose,scavenge excess ROS,and improve pathological features of DR,such as retinal vascular leakage and neovascularization.Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H2O2 signaling pathway and downregulate vital vascular function indicators such as VCAM-1,HIF-1α,and VEGF.These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent,with the potential as a novel multimeric drug for DR therapy.

OBJECTIVE: To compare the efficacy and muscle injury imaging between oblique lateral lumbar interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) in the treatment of single-segment degenerative lumbar spinal stenosis. METHODS: The clinical data of 60 patients with single-segment degenerative lumbar spinal stenosis who underwent surgical treatment from January 2018 to October 2019 was retrospectively analyzed. The patients were divided into OLIF groups and TLIF group according to different surgical methods. The 30 patients in the OLIF group were treated with OLIF plus posterior intermuscular screw rod internal fixation. There were 13 males and 17 females, aged from 52 to 74 years old with an average of (62.6±8.3) years old. And 30 patients in the TLIF group were treated with TLIF via the left approach. There were 14 males and 16 females, aged from 50 to 81 years old with an average of (61.7±10.4) years old. General data including operative time, intraoperative blood loss, postoperative drainage volume, and complications were recorded for both groups. Radiologic data including disc height (DH), the left psoas major muscle, multifidus muscle, longissimus muscle area, T2-weighted image hyperintensity changes and interbody fusion or nonfusion were observed. Laboratory parameters including creatine kinase (CK) values on postoperative 1st and 5th days were analyzed. Visual analogue scale(VAS) and Oswestry disability index(ODI) were used to assess clinical efficacy. RESULTS: There was no significant difference in the operative time between two groups(P>0.05). The OLIF group had significantly less intraoperative blood loss and postoperative drainage volume compared to the TLIF group(P<0.01). The OLIF group also had DH better recovery compared to the TLIF group (P<0.05). There were no significant differences in left psoas major muscle area and the hyperintensity degree before and after the operation in the OLIF group (P>0.05). Postoperativly, the area of the left multifidus muscle and longissimus muscle, as well as the mean of the left multifidus muscle and longissimus muscle in the OLIF group, were lower than those in the TLIF group (P<0.05) .On the 1st day and the 5th day after operation, CK level in the OLIF group was lower than that in the TLIF group(P<0.05). On the 3rd day after operation, the VAS of low back pain and leg pain in the OLIF group were lower than those in the TLIF group (P<0.05). There were no significant differences in the ODI of postoperative 12 months, low back and leg pain VAS at 3, 6, 12 months between the two groups(P>0.05). In the OLIF group, 1 case of left lower extremity skin temperature increased after the operation, and the sympathetic chain was considered to be injured during the operation, and 2 cases of left thigh anterior numbness occurred, which was considered to be related to psoas major muscle stretch, resulting in a complication rate of 10% (3/30). In the TLIF group, one patient had limited ankle dorsiflexion, which was related to nerve root traction, two patients had cerebrospinal fluid leakage, and the dural sac was torn during the operation, and one patient had incision fat liquefaction, which was related to paraspinal muscle dissection injury, resulting in a complication rate of 13% (4/30). All patients achieved interbody fusion without cage collapse during the 6- month follow-up. CONCLUSION Both OLIF and TLIF are effective in the treatment of single-segment degenerative lumbar spinal stenosis. However, OLIF surgery has obviously advantages, including less intraoperative blood loss, less postoperative pain, and good recovery of intervertebral space height. From the changes in laboratory indexes of CK and the comparison of the left psoas major muscle, multifidus muscle, longissimus muscle area, and high signal intensity of T2 image on imaging, it can be seen that the degree of muscle damage and interference of OLIF surgery is lower than that of TLIF.
Male ; Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Retrospective Studies ; Spinal Stenosis/surgery* ; Blood Loss, Surgical ; Lumbar Vertebrae/surgery* ; Spinal Fusion/methods* ; Treatment Outcome ; Pain, Postoperative ; Muscles ; Minimally Invasive Surgical Procedures/methods*

This study aims to explore the anti-depression mechanism of Zuojin Pills based on the plasma constituents, network pharmacology, and experimental verification. UHPLC-TOF-MS was used for qualitative analysis of Zuojin Pills-containing serum. Targets of the plasma constituents and the disease were retrieved from PharmMapper and GeneCards. Then the protein-protein interaction(PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.7.2 was employed construct the "compound-target-pathway" network and the targets and signaling pathways of Zuojin Pills against depression were predicted. CUMS-induced depression mouse model was established to verify the key targets. The results showed that a total of 21 constituents migrating to blood of Zuojin Pills were identified, which were mainly alkaloids. A total of 155 common targets of the constituents and the disease and 67 core targets were screened out. KEGG enrichment and PPI network analysis showed that Zuojin Pills may play a role in the treatment of depression through AMPK/SIRT1, NLRP3, insulin and other targets and pathways. Furthermore, the results of animal experiments showed that Zuojin Pills could significantly improve the depression behaviors of depression, reduce the levels of IL-1β, IL-6 and TNF-α in hippocampus and serum, activate AMPK/SIRT1 signaling, and reduce the protein expression of NLRP3. In conclusion, Zuojin Pills may play a role in the treatment of depression by activating AMPK/SIRT1 signaling pathway, and inhibiting NLRP3 activation and neuroinflammation in the hippocampus of mice.
Animals ; Mice ; Network Pharmacology ; AMP-Activated Protein Kinases ; Chromatography, High Pressure Liquid ; NLR Family, Pyrin Domain-Containing 3 Protein ; Sirtuin 1 ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation

OBJECTIVE: To observe the effect of wheat-grain moxibustion at "Dazhui" (GV 14) on the expressions of Beclin-1 and GRP78 in spinal dorsal horn in rats with cervical spondylotic radiculopathy (CSR), and to explore the possible analgesic mechanism of wheat-grain moxibustion for CSR. METHODS: A total of 48 SD rats were randomly divided into a sham operation group, a model group, a wheat-grain moxibustion group and a wheat-grain moxibustion+3-MA group, 12 rats in each group. The CSR model was prepared by spinal cord insertion method. Three days after modeling, the rats in the model group were intraperitoneally injected with 1 mL of 0.9% sodium chloride solution; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14, 6 cones per time) on the basis of the model group; the rats in the wheat-grain moxibustion+3-MA group were intraperitoneally injected with 3-MA solution and wheat-grain moxibustion at "Dazhui" (GV 14, 6 cones per time). The three groups were intervened for 7 days, once a day. The gait score and mechanical pain threshold were observed before treatment and 7 days into treatment; after the treatment, the expressions of mRNA and protein of Beclin-1 in spinal dorsal horn were detected by real-time fluorescence quantitative PCR and immunohistochemistry; the expression of GRP78 protein in spinal dorsal horn was detected by Western blot method; the autophagosomes and ultrastructure in spinal dorsal horn neurons were observed by electron microscope. RESULTS: After the treatment, compared with the sham operation group, in the model group, the gait score was increased and the mechanical pain threshold was decreased (P<0.01), and the expression of GRP78 protein in spinal dorsal horn was increased (P<0.01). Compared with the model group and the wheat-grain moxibustion+3-MA group, in the wheat-grain moxibustion group, the gait score was decreased and mechanical pain threshold was increased (P<0.01), and the expression of GRP78 protein in spinal dorsal horn was decreased, and the expressions of mRNA and protein of Beclin-1 were increased (P<0.01). Under electron microscope, the ultrastructure of spinal dorsal horn neurons in the wheat-grain moxibustion group was not significantly damaged, and its structure was basically close to normal, and the number of autophagosomes was more than the other three groups. CONCLUSION Wheat-grain moxibustion at "Dazhui" (GV 14) has analgesic effect on CSR rats. The mechanism may be related to moderately up-regulate the expression of Beclin-1, enhance autophagy and reduce endoplasmic reticulum stress.
Animals ; Beclin-1/genetics* ; Endoplasmic Reticulum Chaperone BiP ; Moxibustion ; RNA, Messenger ; Radiculopathy/therapy* ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; Spinal Cord Dorsal Horn ; Spondylosis ; Triticum/genetics*

OBJECTIVE: To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients. METHODS: Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH). RESULTS: Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression. CONCLUSION There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.
Chromosome Aberrations ; Humans ; In Situ Hybridization, Fluorescence ; Multiple Myeloma/genetics* ; Mutation

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ²=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ²=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation ; Child ; Child, Preschool ; Female ; Heart Arrest/therapy* ; Heart Defects, Congenital/therapy* ; Humans ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies

ObjectiveTo establish a simple， fast and accurate method for locating the volatile oil in Angelicae Sinensis Radix based on frozen section and fluorescence imaging technology， and to reveal the distribution and accumulation of volatile oil in the roots of this herbal medicine. MethodAngelicae Sinensis Radix was used as the research material， the best frozen section conditions for the research material were established by comparing the effects of different cryoprotectants on the quality of frozen sections of Angelicae Sinensis Radix. The suitability of Sudan Ⅲ chemical staining and fluorescence localization for positioning the volatile oil were compared according to the loss of volatile oil and the complexity of operation process. ResultA new method for evaluating the quality of frozen sections of Angelicae Sinensis Radix was established. According to the evaluation equation， it was found that the highest score was obtained when the head， body and tail positions of Angelicae Sinensis Radix were treated with 20% glycerol， 15% glycerol and 20% sucrose， respectively. There was yellowish-brown oily substance in the oil chambers of phelloderm and secondary phloem， and oil canal of the secondary xylem of Angelicae Sinensis Radix， which could be stained orange red or orange yellow by Sudan Ⅲ， and there was green spontaneous fluorescence in the same part under the fluorescence microscope. ConclusionThe relatively complete section of Angelicae Sinensis Radix can be obtained after being treated with cryoprotectant. The volatile oil exists in the oil chambers of phelloderm and secondary phloem， and oil canal of the secondary xylem of Angelicae Sinensis Radix. This study can provide reference for observation of the accumulation sites of volatile oil in other plants.

Objective:To rapidly identify the chemical constituents in Xiao Chengqitang by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry （UPLC-Q-Orbitrap-MS）. Method:The method was established by the Waters CORTECS T3 column （2.1 mm×150 mm， 1.6 μm）， mobile phase was methanol （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-5 min， 3%-21%A； 5-20 min， 21%-36%A； 20-32 min， 36%-50%A； 32-42 min， 50%-62%A； 42-50 min， 62%-85%A； 50-60 min， 85%-95%A）， the flow rate was 0.2 mL·min^-1， and the column temperature was 30 ℃. UPLC-Q-Orbitrap-MS was operated in positive and negative ion modes， the scanning range was 100-1 200 with mode of Full MS/dd-MS²， and the collision energies were 20， 40 eV. The compounds were identified by comparing with reference substances and combining with literature reports and MS database information. Result:A total of 123 components were identified in Xiao Chengqitang， including 33 flavonoids， 25 anthraquinones and anthrones， 23 phenylpropanoids， 15 tannins， 10 nitrogen-containing components and 17 other components. Among them， 32 components were determined by reference substances. Conclusion:The material basis of Xiao Chengqitang is flavonoids， anthraquinones and anthrones， phenylpropanoids， which is derived from Aurantii Fructus Immaturus， Rhei Radix et Rhizoma and Magnoliae Officinalis Cortex， respectively.