ObjectiveTo explore the mechanism and pathway of Gandou Fumu decoction （GDFMD） in the development of liver fibrosis in Wilson's disease （WD）. MethodFirst， 30 TX-j mice were randomly divided into the model group， high-dose， medium-dose， and low-dose GDFMD groups， and penicillamine group， with six mice in each group， and another six wild-type mice were used as the normal group. The high-dose， medium-dose， and low-dose GDFMD groups were intragastrically administered drugs of 13.92， 6.96， 3.48 g·kg^-1. In the penicillamine group， 0.1 g·kg^-1 of penicillamine was given by intragastric administration. The model group and the normal group were given equal volume of normal saline， once a day， for four consecutive weeks. Samples were collected four weeks after gavage， and enzyme-linked immunosorbent assay （ELISA） was used to detect type Ⅲ procollagen peptide （PCⅢ）， collagen type Ⅳ （Col Ⅳ）， hyaluronic acid （HA）， and laminin （LN）. Hematoxylin-eosin （HE）， Masson， and picric acid-Sirus red collagen （Sirus Red） staining were used to observe the histopathological changes of liver fibrosis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， immunohistochemistry， and Western blot were used to observe the expressions of α-smooth muscle actin （α-SMA） and collagen type Ⅰ （Col Ⅰ）， which were related to the activation of hepatic stellate cells （HSCs）. The expression of miR-29b-3p was observed by Real-time PCR. The expression of Unc-51-like kinase 1 （ULK1） and its downstream-related factors were observed by Western blot. The downstream genes of miR-29b-3p were verified by the dual luciferase reporter gene detection method. ResultCompared with the normal group， the four items of liver fibrosis （PCⅢ， Col Ⅳ， HA， and LN） in the model group were significantly abnormal （P<0.01）， and the pathology was significantly abnormal. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was up-regulated （P<0.05， P<0.01）， and miR-29b-3p expression was down-regulated （P<0.01）. ULK1， p-ULK1， autophagy-related gene 13 （Atg13）， p-Atg13， Beclin-1， FAK family kinase-interacting protein of 200 kDa （FIP200）， activating molecule in BECN1-regulated autophagy protein 1 （AMBKA1）， and microtubule-associated protein 1 light chain 3Ⅱ/Ⅰ（LC3Ⅱ/Ⅰ） were up-regulated （P<0.05， P<0.01）. p62 protein expression was down-regulated （P<0.01）. Compared with the model group， the four items of liver fibrosis in the high-dose， medium-dose， and low-dose GDFMD groups and the penicillamine group were significantly improve （P<0.01）， and the pathological conditions were improved. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was down-regulated （P<0.05， P<0.01）， and the expression of miR-29b-3p was up-regulated （P<0.01）. ULK1， p-ULK1， Atg13， p-Atg13， Beclin-1， FIP200， AMBKA1， and LC3Ⅱ/Ⅰ were down-regulated （P<0.05， P<0.01）， and p62 protein expression was up-regulated （P<0.01）. The prediction software predicted that there was a binding site between miR-29b-3p and ULK1. The dual-luciferase reporter gene detection method indicated that the luciferase activity of the ULK1-WT plasmid-transfected cell group was reduced when miR-29b-3p mimics were co-cultured （P<0.01）. ConclusionGDFMD can regulate ULK1-mediated autophagy by up-regulating miR-29b-3p and further exert its anti-hepatic fibrosis effect in Wilson's disease.

Objective To explore the mechanism of dendrobine in the treatment of diabetic kidney disease(DKD)by intervening immunity using network pharmacology,bioinformatics and Western blot.Methods The targets of dendrobine were screened by Pharmmaper,Superpred and other databases.The disease targets of DKD were screened from GeneCards,OMIM and other databases.The immune-related targets were searched in Immport,In-nateDB and other databases.The intersection of the above three was obtained via Venn diagram.The PPI map of intersection targets was constructed by STRING software combined with Cytoscape software,and the core targets in the interaction network were mined by CytoHubba plug-in.The data set GSE142025 was obtained from GEO,and immune infiltration and WGCNA analysis were performed using the R language CIBERSORT package.GSE1009,GSE30122 and GSE142025 were used for gene differential expression analysis and ROC verification.The correla-tion between core targets and immune cell phenotype was analyzed.Molecular docking and molecular dynamics sim-ulation analysis were used to test the binding force of dendrobine to key targets.Western blot was used to detect the expression of HSP90AA1 in HK-2 cells.Results A total of 128 intersecting genes,including HSP90AA1,LCK and EGFR,were obtained,and the core targets involved HSP90AA1,LCK and STAT3;molecular docking and molecular dynamics simulation analyses showed that the protein of HSP90AA1 could bind well with dendrobine.Western blot experiments showed that compared with the control group,HSP90AA1 was significantly down-regula-ted in the high glucose group.Compared with the high glucose group,HSP90AA1 was significantly up-regulated in the dendrobine group.Conclusion Dendrobine can intervene in diabetic kidney disease by regulating the expres-sion of HSP90AA1.

Objective:To carry out prenatal diagnosis for a fetus with Meckel syndrome(MKS) and explore its genetic basis.Methods:A pregnant woman presented at Suzhou Municipal Hospital in February 2018 was selected as the study subject. Clinical data was collected. Muscle tissue sample from the abortus and peripheral blood samples from the couple were collected. Genomic DNA was extracted and subjected to chromosomal microarray analysis (CMA) and whole exome sequencing. Candidate variant was verified by Sanger sequencing.Results:The fetus was found to have microcephaly, oligohydramnios, polycystic kidneys and banana-shaped cerebellum at 18 weeks of gestation. After induction of labor, it was found to have encephalocele, renal cysts and polydactyly. CMA has found no abnormality. Whole exome sequencing revealed novel compound heterozygous variants c. 296delA (p.Lys99SerfsTer6) and c. 1243G>A (p.Val415Met) in the TMEM67 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 296delA variant was predicted to be pathogenic (PVS1+ PM2_Supporting+ PP4), whilst the c. 1243G>A variant was predicted to be likely pathogenic (PM2_Supporting+ PM3+ PP3_Moderate+ PP4). Conclusion:The c. 296delA and c. 1243G>A compound heterozygous variants of the TMEM67 gene probably underlay the MKS in this fetus.

Objective To explore the characteristics of response inhibition of military university students during multitasking operation. Methods Repeated measures of ANOVA as well as distribution test were employed to explore how the performance of 127 military university students in Go/No-Go test was affected by simulated driving task. Results The test results of 127 participants showed that there was a interaction between the interference task and the Go trial proportion on the hit rate and false alarm rate,that is,no significant difference was observed between the 60％ and 40％ of trial proportion without interference task (both P>0.05),but the hit rate and false alarm rate in the 60％ trial proportion condition were significantly higher than those in the 40％ trial proportion condition under interference task (both P<0.01).In addition,significant main effects of interference task were observed on hit rate,false alarm rate,and discrimination index d' (all P<0.01),that is,the interference task reduced the hit rate and discrimination,but increased the false alarm rate.Moreover,individual differences existed in the discrimination index d' changes,and the participants were divided into easily disturbed group (n=23,18.11％),undisturbed group (n=20,15.75％),and intermediate group (n=84,66.14％) by adding or subtracting 1 standard deviation from the mean of the difference. Conclusion The interference tasks increase the psychological load of military university students during multitasking operation,and impair the response inhibition;and individual differences exist in response inhibition.

Objective:To explore the value of adenosine loaded 99Tc m-MIBI single photon emission computed tomography (SPECT) in evaluating the therapeutic effect of nicorandil on coronary microvascular angina (CMVA). Methods:Sixty eight patients diagnosed with CMVA in the Second Affiliated Hospital of Xuzhou Medical University from January 2021 to March 2022 were selected and randomly divided into a control group and a nicorandil group, with 34 patients in each group, using a random number table method. The control group received isosorbide mononitrate in addition to conventional treatment, while the nicorandil group received nicorandil in addition to conventional treatment. Both groups were treated continuously for 3 months. All patients underwent adenosine loading 99Tc m-MIBI SPECT before and after treatment to measure the degree of myocardial perfusion defect (SDS), myocardial perfusion defect area (SRS), and degree of improvement of myocardial perfusion defect (SIS). Clinical symptoms, electrocardiogram changes, myocardial enzyme indicators [cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH)], hemodynamic parameters [systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), stroke volume (SV), cardiac output (CO), peripheral resistance (TPR), left ventricular work index (LVWI), and myocardial oxygen consumption (MVO 2)] were evaluated. Results:After treatment, the SDS and SRS of the nicorandil group were significantly lower than those of the control group ( P<0.01), and the SIS was significantly higher than that of the control group (all P<0.01); The improvement of abnormal myocardial perfusion imaging was significantly better than that of the control group (χ 2=4.976, P<0.05); the frequency, duration, and severity of angina attacks, Canadian Heart Association (CCS) grading, and incidence of ischemic changes on electrocardiogram were all lower than those of the control group ( P<0.01); The levels of serum cTnI, CK-MB, and LDH were significantly lower than those in the control group (all P<0.01); SBP, DBP, HR, LVWI, and MVO 2 were significantly lower than those in the control group (all P<0.01), while SV and CO were significantly higher than those in the control group (all P<0.01). Conclusions:Adenosine loaded 99Tc m-MIBI SPECT can effectively evaluate the therapeutic effect of nicorandil on CMVA, and nicorandil can improve myocardial perfusion defects and clinical manifestations in CMVA patients.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

OBJECTIVE: To evaluate the value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for assessing disease activity in patients with rheumatoid arthritis (RA) treated with tofacitinib. METHODS: This retrospective study was conducted among 98 RA patients in active stage treated with tofacitinib in Third Xiangya Hospital and 100 healthy control subjects from the Health Management Center of the hospital from 2019 to 2021. We collected blood samples from all the participants for measurement of erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and other blood parameters 1 month before and 6 months after tofacitinib treatment. We further evaluated PLR and NLR before and after tofacitinib treatment in the RA patients, and analyzed their correlations with RA disease activity. RESULTS: PLR and NLR increased significantly in RA patients as compared with the healthy controls. In the RA patients, PLR and NLR were positively correlated with the levels of hs- CRP, ESR, IL- 6, Disease Activity Score of 28 joints-ESR (DAS28-ESR), anti-cyclic citrullinated peptide (CCP), and rheumatoid factor (RF) before and after tofacitinib treatment. Tofacitinib treatment for 6 months significantly decreased hs-CRP, ESR, IL-6, CCP, RF and DAS28-ESR levels in the RA patients. CONCLUSION NLR and PLR can be useful biomarkers for assessing disease activity in RA patients treated with tofacitinib.
Humans ; Neutrophils ; Retrospective Studies ; C-Reactive Protein/analysis* ; Interleukin-6/metabolism* ; Arthritis, Rheumatoid ; Lymphocytes

Objective:To investigate the anatomical basis for the preparation of the profunda artery perforator flap (PAPF) in the posteromedial femoral region and its application in the reconstruction of oral and maxillofacial defects.Methods:Six lower limbs of Chinese adult cadavers were micro-surgically dissected. CT angiography (CTA) data of bilateral lower limbs of 6 patients was also collected retrospectively. The number, external diameter, pedicle length, and distribution of perforators in the posteromedial femoral region were recorded from the specimens and CTA data. Meanwhile, 10 patients with oral squamous cell carcinoma in the Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University from August 2018 to June 2021 were treated with the PAPF. At each follow-up, contour and function of recipient and donor site, as well as swallowing and speech function were evaluated.Results:A total of 19 profunda artery perforator were identified in 6 lower limb specimens. The outer diameter at the beginning of the source artery was (2.34±0.25) mm and the total length of the pedicle was (11.12±1.06) cm. CTA data analysis of 12 legs identified 15 perforators of profunda artery in the posteromedial region. Eleven perforators were septocutaneous, including 2 perforators with a common trunk, while the remaining 4 perforators were musculocutaneous. As for different patterns of perforators (septocutaneous perforators, musculocutaneous perforators and perforators with a common trunk), the longitudinal distance to the pubic tubercle was (19.95±2.43), (21.84±2.54) and (19.48±0.55) cm respectively. The horizontal distance to the posterior edge of gracilis was (3.54±1.10), (3.72±0.30) and (3.85±1.48) cm, respectively. The initial diameters of perforators was (2.4±0.4), (2.6±0.6) and 1.9 mm respectively. Ten cases of the profunda artery perforator flaps survived successfully after operation. The flap sizes ranged from 8 cm×6 cm to 12 cm×7 cm. The patients were evaluated at 1, 3 and 6 months, and with 6 months interval ever since. During the follow-up, the shape of the recipient site was ideal, and the swallowing and language functions were not significantly affected. There was only linear scar in the donor area, and the function of the thigh was basically normal.Conclusions:PAPF possessed a good anatomic stability, suitable vascular pedicle length and diameter, minor influence to the donor area, sufficient amount tissue with good quality. It is an ideal choice for head and neck reconstruction.

Liver fibrosis is the initial stage of the development of various chronic liver diseases into liver cirrhosis and is a reversible process. As a subset of extracellular vesicles that can carry active substances such as proteins, lipids, and RNA, exosomes are involved in intercellular signal communication and have attracted more and more attention in recent years. Studies have shown that non-coding RNAs in exosomes play an important role in the development and progression of liver fibrosis. This article discusses the mechanism of action of exosome long non- coding RNAs (including MALAT1, H19, GAS5, MEG3, PVT1, and P21), exosome short non-coding RNAs (including micro-RNA, small nucleolus RNA, PIWI-interacting RNA, and small interference RNA), and exosome circular RNA in the development and progression of liver fibrosis, and it is concluded that exosomes from different sources (such as hepatocytes and cholangiocytes) carrying non-coding RNAs mainly affect the activation, proliferation, migration, and transformation of hepatic stellate cells. In-depth studies of exosome non-coding RNAs in the future are expected to find potential new targets for the treatment of liver fibrosis.

Objective:To evaluate the role of spinal peroxisome proliferation-activated receptor-γ (PPAR-γ) in protectin D1 (PD1)-induced reduction of neuropathic pain (NP) in rats.Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-250 g, were divided into 4 groups ( n=12 each) by a random number table method: sham operation group (Sham group), NP group, NP plus PD1 group (NP+ PD group), and NP plus PD1 plus GW9662 group (NP+ PD+ GW group). Neuropathic pain was induced by spared nerve injury in anesthetized rats.In NP+ PD and NP+ PD+ GW groups, PD1 900 ng (diluted to 20 μl in dimethyl sulfoxide [DMSO]) was intrathecally injected once a day for 8 consecutive days starting from 30 min before establishing the model.In NP+ PD+ GW group, the PPAR-γ antagonist GW9662 200 ng (diluted to 20 μl in DMSO) was intrathecally injected once a day for 8 consecutive days starting from 45 min before establishing the model.The equal volume of DMSO was intrathecally injected in Sham group.The mechanical paw withdrawal threshold (PWT) was measured before establishing the model and at 1, 3, 5, 7, 10 and 14 days after establishing the model.Six rats in each group were sacrificed on day 14 after establishing the model, and their lumbar enlargements were removed for determination of the expression of PPAR-γ, TNF-α and IL-6 by Weston blot.Six rats in each group were sacrificed on day 14 after establishing the model, L 4, 5 segments of the spinal cord were removed, and the co-expression of PPAR-γ with neuron-specific nucleoprotein (NeuN), glial fibrillary acidic protein (GFAP) or serum calcium binding adapter molecule 1 (Iba-1) was determined by immunofluorescence staining. Results:Compared with group Sham, PWT was significantly decreased at each time point after establishing the model, the expression of PPAR-γ was down-regulated, and the expression of TNF-α and IL-6 was up-regulated in the other three groups ( P<0.05). Compared with group NP, PWT was significantly increased at 7-14 days after establishing the model, the expression of PPAR-γ was up-regulated, and the expression of TNF-α and IL-6 was down-regulated in group NP+ PD, and no significant change was found in the parameters mentioned above in group NP+ PD+ GW ( P>0.05). Compared with group NP+ PD, PWT was significantly decreased at 7-14 days after establishing the model, the expression of PPAR-γ was down-regulated, and the expression of TNF-α and IL-6 was up-regulated in group NP+ PD+ GW ( P<0.05). The results of immunofluorescence staining of the spinal cord showed that PPAR-γ was co-expressed with NeuN and GFAP. Conclusion:The mechanism by which PD1 mitigates NP is related to promoting the activation of PPAR-γ in spinal cord neurons and astrocytes and inhibiting inflammatory responses in rats.