BACKGROUND:There are differentially expressed genes in acute intracerebral hemorrhage,which are related to the occurrence and development of intracerebral hemorrhage. OBJECTIVE:To screen differentially expressed genes and key genes in brain tissue of a rat model with acute intracerebral hemorrhage,to validate them through qPCR,and to analyze the relationships between key genes and the neurological function and brain tissue water content after intracerebral hemorrhage. METHODS:Seventy-eight Sprague-Dawley rats were randomly divided into two groups:in intracerebral hemorrhage group,a rat model of acute intracerebral hemorrhage was made using collagenase injection at the right caudate nucleus;and in sham-operated group,rats were injected with equal amount of saline at the same site.RNA was extracted from rat brain tissues of both groups using the TRIzol method and transcriptome sequencing technology was used to identify differentially expressed genes in brain tissues of acute intracerebral hemorrhage,which were then verified by qPCR and analyzed for the relationships between the genes and neurological function and brain tissue water content after intracerebral hemorrhage.And the key genes were analyzed by GO and KEGG functional enrichment analysis in combination with bioinformatics. RESULTS AND CONCLUSION:Ten key genes were identified,including CXCL8,SERPINE1,TFPI2,CXCR4,GDA,KCNQ5,ERICH3,SCN3B,CACNA1E,and CCL20.The contents of GDA,KCNQ5,ERICH3,SCN3B,and CACNA1E in the intracerebral hemorrhage group were lower than those in the sham-operated group(P＜0.05).The contents of CXCL8,SERPINE1,TFPI2,CXCR4 and CCL20 in the intracerebral hemorrhage group were higher than those in the sham-operated group(P＜0.05).The contents of GDA,KCNQ5,ERICH3,SCN3B,and CACNA1E were positively correlated with brain tissue water content and neurologic deficit score(P＜0.05),while the contents of CXCL8,SERPINE1,TFPI2,CXCR4 and CCL20 were negatively correlated with brain tissue water content and neurologic deficit score(P＜0.05).GO analysis indicated that differentially expressed genes were mainly enriched in two biological processes(leukocyte chemotaxis and chemokine-mediated signaling pathways),two cell components(cation channel complexes and ion channel complexes),and two molecular functions(gated channel activity and ion channel activity).KEGG analysis indicated that differentially expressed genes were concentrated in tumor necrosis factor signaling pathway,glutamatergic synapses and GABAergic synapses.To conclude,the differentially expressed genes in intracerebral hemorrhage include CXCL8,SERPINE1,TFPI2,CXCR4,GDA,KCNQ5,ERICH3,SCN3B,CACNA1E,and CCL20,and these genes are related to brain tissue water content and neurological function after intracerebral hemorrhage.These genes are mainly enriched in cell components,binding functions,cellular protrusions,and other related biological functions.

BACKGROUND:Internal heat-type acupuncture therapy is a new treatment technique that combines acupuncture therapy with hyperthermia.It has good clinical effects on steroid-induced osteonecrosis of the femoral head,but the mechanism of action is still not fully clear. OBJECTIVE:To explore the possible mechanism of internal heat-type acupuncture therapy in treating steroid-induced osteonecrosis of the femoral head in rabbits. METHODS:Thirty-two New Zealand rabbits were randomly divided into blank group,model group,internal heat-type acupuncture group and shock wave group using a random number table method,with 8 rabbits in each group.The model group,internal heat-type acupuncture group and shock wave group were modeled using methylprednisolone sodium succinate combined with Escherichia coli endotoxin.The internal heat-type acupuncture group received an internal heat-type acupuncture intervention on the buttocks of rabbits,once a week,for 20 minutes each time.The shock wave group received shock wave intervention on the buttocks of rabbits,once a week,with 2 000 beats per session.The blank group and model group were not given any treatment.After 4 weeks of intervention,blood samples and bilateral femoral head samples were collected from experimental rabbits.The levels of tumor necrosis factor-α and interleukin-6 in serum were detected by ELISA;the histomorphology of the femoral head was observed using hematoxylin-eosin staining and the rate of empty lacunae was calculated;the protein expressions of matrix metalloproteinase 2,matrix metalloproteinase 9,matrix metalloproteinase tissue inhibitor 1,and matrix metalloproteinase tissue inhibitor 2 were detected by immunohistochemistry and western blot. RESULTS AND CONCLUSION:Compared with the blank group,the model rabbits showed reduced food intake,mental fatigue,and decreased activity;compared with the model group,the above performance of the experimental rabbits was significantly improved after internal heat-type acupuncture and shock wave treatment.Compared with the blank group,the histomorphology of the femoral head in the model group deteriorated significantly and the rate of empty bone lacuna increased(P<0.001),while the histomorphology of the femoral head in the internal heat-type acupuncture group and shock wave group was significantly improved compared with the model group,and the rate of empty bone lacuna was reduced(P<0.001).The serum levels of tumor necrosis factor-α and interleukin-6 in the model group were significantly higher than those in the blank group(P<0.05),while the serum levels of tumor necrosis factor-α and interleukin-6 in the internal heat-type acupuncture group and the shock wave group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 in the femoral head of the model group were significantly increased,while the expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly decreased(P<0.001);compared with the model group,the protein expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 were significantly decreased,while the protein expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly increased in the internal heat-type acupuncture group and the shock wave group(P<0.001).Overall,these findings indicate that internal heat-type acupuncture may promote the repair of the necrotic femoral head by regulating the levels of matrix metalloproteinases/matrix metalloproteinase tissue inhibitors and serum inflammatory factors,thus treating early steroid-induced osteonecrosis of the femoral head.

In recent years， the research data on the combination model of insomnia of liver depression and qi stagnation syndrome in traditional Chinese medicine （TCM） were sorted out and summarized in terms of the selection of experimental animals， modelling methods， and model evaluation， with a view to providing references for the standardized preparation of the experimental model of insomnia of liver depression and qi stagnation syndrome and the study of the intervention mechanism. As for the selection of experimental animals， rats and mice are commonly used for the study of sleep patterns in the insomnia model of liver depression and qi stagnation syndrome because their sleep patterns are similar to those of human beings； zebrafish is suitable for the study of sleep patterns in early development because of its high genetic homology； and rhesus macaques， common marmosets， and crab-eating monkeys are used for the study of highly complex sleep disorders because their physiological and behavioural characteristics are closer to those of human beings. In terms of modelling methods， electrical stimulation， chronic restraint， chronic emotional stress and impact psychological stress each have their own characteristics and application scenarios， while chronic tail-clamping stimulation combined with intraperitoneal injection of p-chlorophenylalanine （PCPA） combines physical and chemical stimuli， in order to simulate the complex mechanism of insomnia in human beings， and to more comprehensively simulate the pathology of insomnia with liver depression and qi stagnation syndrome. In terms of evaluation indexes， electroencephalography （EEG） and electromyography （EMG） monitoring and barbiturate synergistic sleep test are the most commonly used and scientific methods for evaluating insomnia animal models with liver depression and qi stagnation syndrome， which can provide intuitive and continuous sleep state monitoring； barbiturate synergistic sleep test can reflect the sensitivity and responsiveness of the model animals to the sleep-regulating medications； and the introduction of the method of using formulas to measure syndromes for the evaluating the model can combine the treatment and diagnostic principles of TCM with modern scientific research.

Fatigue is one of the common symptoms in patients with liver cirrhosis, which has a serious impact on the quality of life of patients. This article reviews the influencing factors and intervention strategies of fatigue in patients with cirrhosis, aiming to provide reference for early recognition and intervention of fatigue in patients with cirrhosis.

Anti-glomerular basement membrane (GBM) nephritis and anti-neutrophil cytoplasmic antibody (ANCA) -associated vasculitis are both autoimmune diseases that can involve multiple systems throughout the body, and both can cause crescent glomerulonephritis. At present, cases of such "double-positive" antibodies have been reported at home and abroad , but the cases of acute progressive glomerulonephritis (RPGN) with IgA nephropathy that are both positive for GBM and ANCA are relatively rare. This case was a middle-aged female patient, whose clinical manifestations were consistent with rapidly progressive glomerulonephritis, positive for anti-GBM antibodies and anti-myeloperoxidase. After renal puncture biopsy, she was diagnosed as anti-GBM nephritis complicated with ANCA associated vasculitis and IgA nephropathy.After treatment with plasma exchange, hemodialysis, glucocorticoids, cyclophosphamide, etc., the condition improved and the patient was discharged. But the patient did not follow the doctor's instructions to take medication and continue hemodialysis treatment after discharge, and the condition worsened, ultimately leading to death.

ObjectiveTo explore the efficacy of acupuncture intervention for children with monocular refractive-parallax amblyopia and the possible mechanisms of brain function based on resting-state functional magnetic resonance （rs-fMRI）. MethodsSeventy-six children with anisometropic amblyopia were randomly divided into routine treatment group （38 cases） and acupuncture treatment group （38 cases）. In the conventional group， the children were given three regular treatments of red flash， grating and visual stimulation for 5 mins each time； in the acupuncture group， on the basis of the conventional treatment， the children were given acupuncture for 20 mins each time on bilateral Jingming （BL 1）， Cuanzhu （BL 2）， Guangming （GB 37） and Fengchi （GB 20）； the children in both groups were treated once every other day and three times a week for 4 weeks. The corrected visual acuity was compared between groups before and after treatment. Fifteen children with left-sided refractive amblyopia were randomly selected from each of the above two groups and underwent brain rs-fMRI scans before and after treatment， and 10 healthy children with normal visual acuity of the matched gender and age were included in the normal group and underwent brain rs-fMRI scans. Based on the activation likelihood estimation （ALE） method， we constructed the what visual pathway network， and compared and analyzed the spherical regions of interest （ROIs） of the children with normal children， and both groups of children with differences in functional connectivity （FC values） within the what pathway in the brain before and after treatment. ResultsTwo cases dropout in the acupuncture group， and finally 36 cases in the acupuncture group and 38 cases in the conventional group were included in the analysis. Compared with before treatment， the best corrected visual acuity of amblyopia in both groups was significantly improved after treatment （P＜0.05）， and the improvement of vision in the acupuncture group was significantly better than that in the conventional group （P＜0.05）. The results of rs-fMRI showed that the FC values of the primary optic cortex and the right fusiform gyrus， the left lingual gyrus and the right fusiform gyrus， and the right infraoccipital gyrus and the right middle temporal gyrus were significantly elevated in the brain of the refractive amblyopia children with the whitepathic amblyopia， compared with that of the normal children （P＜0.05）. The FC values of the left lingual gyrus， the right suboccipital gyrus with the right fusiform gyrus， the left lingual gyrus with the right middle temporal gyrus， the right and left lateral middle occipital gyrus， and the right and left lateral middle occipital gyrus with the right suboccipital gyrus were significantly （P＜0.05） lower in the conventional group compared with those in the conventional group before treatment. Compared with that before acupuncture treatment， the FC values of the right lingual gyrus and the right fusiform gyrus， the primary visual cortex and the right middle temporal gyrus increased significantly after acupuncture treatment （P＜0.05）， and the FC values of the left inferior occipital gyrus and the right middle temporal gyrus， the FC values of the left lingual gyrus and the right middle occipital gyrus decreased significantly （P＜0.05）. Compared between groups after treatment， the FC between the left suboccipital gyrus and the right fusiform gyrus in the acupuncture group was significantly higher than that in the conventional group （P＜0.05）， and the FC between the left middle occipital gyrus and the right and left suboccipital gyrus was significantly lower than that in the conventional group （P＜0.05）. ConclusionAcupuncture can significantly improve the corrected vision of anisometropic amblyopic children， and its effect mechanism may focus on regulating the occipito-temporal interlobular functional connectivity within the what pathway， thus improving the children's visual function of shape and color vision and visual learning and memory ability.

Objective:To study the clinical features, genetic characteristics and prognosis of neonatal diabetes mellitus (NDM).Methods:From January 2015 to January 2022, neonates with NDM admitted to the Department of Neonatology of our hospital were retrospectively reviewed.Their clinical manifestations, biochemical data, genetic tests, treatments and outcomes were analyzed.Results:A total of 6 cases with NDM were included, with 3 males and 3 females. All 6 cases were full-term infants, 5 were low birth weight infants and 1 had family history of diabetes. High blood glucose were found on 1~11 d (average 4 d) after birth. 3 cases were diagnosed during blood glucose screening for low birth weight and 3 cases were diagnosed due to infection and/or diabetic ketoacidosis. Blood C-peptide levels were below normal range in all 6 cases. Blood insulin levels were decreased in 5 cases and remained at the lower limit of normal range in 1 case. All infants received genetic tests and 4 showed abnormal results, including 2 cases of ABCC8 gene mutation [c.2060C>T (p.T687M), not reported; c.674T>C (p.L225P), reported], 1 case of KCNJ11 gene mutation [c.602G>A (p.Arg201His), not reported] and 1 case of paternal uniparental disomy (UPD)6q24 (reported). All 6 cases were treated with insulin. Glibenclamide was experimented to replace insulin in 3 cases and 1 case was successful. During follow-up (at the age 4 months~5 years old), 4 cases were diagnosed with transient NDM, 1 case with permanent NDM and 1 case died at the age of 4 months without classification. 1 case showed psychomotor and language delay and the others had otherwise normal development.Conclusions:Most NDM infants are low birth weight infants with reduced blood insulin and C-peptide.Transient NDM are common. Proactive genetic testing may help treatment.

Objective:To explore any effect of supplementing low-frequency repeated transcranial magnetic stimulation (rTMS) with intermittent resistance training on muscle tone and the recovery of motor function among persons with Parkinson′s disease (PD).Methods:A total of 104 PD patients were randomly divided into an observation group and a control group, each of 52. Both groups were treated with conventional drugs and low-frequency rTMS, while the observation group was additionally provided with intermittent resistance training for 8 weeks. Before and after the intervention, the motor functioning of both groups was evaluated using unified Parkinson′s disease rating scale-III (UPDRS-III) and the Berg Balance Scale (BBS). Limb muscle tension was quantified using the modified Ashworth scale (MAS). The subjects′ psychological states were quantified using the exercise self-efficacy scale (ESE), and the modified Barthel index (MBI) was applied to evaluate their ability in the activities of daily living. A 3D motion processing system collected and analyzed data describing each subject′s gait kinematics.Results:After the intervention, significantly greater average improvement was observed in all of the outcome measures among the observation group compared with the control group.Conclusion:Combining intermittent resistance training with low-frequency rTMS can significantly reduce muscle tone and improve the motor functioning of PD patients. The combination is more effective than low-frequency rTMS alone.

Objective To investigate the effects of endothelial progenitor cells(EPC)-derived microp-articles(MPs)with different injury treatments on EPC.Methods EPC cells were cultured and EPCs were i-dentified by flow cytometry.EPCs were treated with high glucose(HG)and tumor necrosis factor(TNF)-a recombinant protein,and MPs were extracted.The structural changes of microtubules,Golgi bodies and other organelles in EPC were observed by transmission electron microscopy.MTT assay was used to detect cell pro-liferation.Cell scratch assay was used to evaluate cell migration ability.Cell lumen formation assay was used to detect lumen formation.The expression levels of endothelial nitric oxide synthase(eNOS),silent informa-tion regulator 1(SIRT1),rat sarcoma(RAS)and extracellular regulated protein kinase(ERK)in EPC after different treatments were detected by quantitative real-time fluorescence PCR(qPCR)and Western blot.Re-sults Compared with the control-EPC-MPs group,the microtubule structure of the HG-EPC-MPs group and the TNF-α-EPC-MPs group was complete,the length was shortened,and the Golgi structure was relatively complete.Compared with the control-EPC-MPs group,the proliferation rate of EPC in the HG-EPC-MPs group and the TNF-α-EPC-MPs group was down-regulated,the cell migration ability was decreased,and the tube formation was decreased(P＜0.05).Compared with the control-EPC-MPs group,the mRNA and protein expressions of eNOS,SIRT1,RAS and ERK in the HG-EPC-MPs group and the TNF-α-EPC-MPs group were down-regula-ted(P＜0.05).Conclusion HG and TNF-α mediated MPs derived from EPC injury may change the structure of organelles in EPC by regulating the expression of SIRT1/ERK1 pathway proteins,thus affecting the biolog-ical function of EPC.

Objective:To evaluate the efficacy of Janus kinase (JAK) inhibitors in the treatment of 5 children with severe alopecia areata, especially those with complicated nail damage.Methods:A total of 5 children with severe alopecia areata were enrolled and treated with oral JAK inhibitors (tofacitinib or baricitinib). The improvement of hair loss was assessed by using the severity of alopecia tool (SALT) at 12, 24, 36, and 48 weeks after the start of treatment. For 3 children with complicated nail damage, the improvement of diseased nails and toenails was evaluated by using the modified nail psoriasis severity index after treatment. During the treatment, adverse reactions were monitored.Results:The 5 children with severe alopecia areata were aged 2 - 11 years, with the disease duration ranging from 5 to 120 months, and the treatment with JAK inhibitors lasted 24 - 48 weeks. After 12-week treatment, 2 children achieved a 50% improvement in SALT (SALT50) ; after 24-week treatment, 3 achieved SALT95, and 1 achieved SALT75 and then withdrew baricitinib for personal reasons; after 36-week treatment, 3 achieved SALT99, and then received half-dose treatment; after 48-week treatment, 1, 1, 1 and 1 patient achieved SALT99, SALT83, SALT31, and SALT0, respectively, and 2 of them experienced gradually aggravated hair loss 1 - 2 months after the start of half-dose treatment. Among the 3 children with complicated nail damage, the improvement rates of nail severity index scores were 67.5%, 45.4%, and 25% respectively, and the improvement rates of toenail severity index scores were 42.5%, 71.4%, and 5% respectively after 12-week treatment; after 48-week treatment, the improvement rate of nail severity index scores were 100%, 100%, and 50% respectively, and the improvement rate of toenail severity index scores were 96.2%, 100%, 50% respectively. During the treatment, the uric acid level increased in 2 children, and one of them was accompanied by increased serum levels of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol; 1 suffered from respiratory tract infections twice during the treatment, and was recovered after symptomatic treatment; there were no adverse reactions leading to drug withdrawal.Conclusion:JAK inhibitors can be used as a treatment option for severe alopecia areata in children.