Objective:To investigate the effect of Yiqi Shengqing Formula on neuronal damage in ischemic stroke(IS)rats by regulating brain-derived neurotrophic factor(BDNF)-extracellular regulated protein kinase(ERK)-cyclic adenosine monophosphate-responsive element binding protein(CREB)signal pathway.Methods:IS rat model was prepared by modified thread suppository method,and randomly divided into model group,low dose Yiqi Shengqing Formula(3 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)+empty load group,high dose Yiqi Shengqing Formula(6 g/kg)+BDNF knockdown group,with 10 rats in each group,another 10 healthy rats were set as sham operation group.After intervention with Yiqi Shengqing Formula and plasmid,neural function of rats in each group was scored with Longa scoring method;Morris water maze test was used to detect cognitive impairment of rats in each group;Nissl staining was used to detect the number of neurons in ischemic peripheral brain tissue and hippocampus of rats in each group;synaptic morphology of ischemic peripheral brain tissue was detected by silver staining;levels of TNF-α and IL-8 in brain tissue and serum of rats in each group were measured by ELISA;expressions of BDNF-ERK-CREB signal pathway related proteins in rat brain were detected by Western blot.Results:Compared with sham operation group,synaptic morphology of ischemic peripheral brain tissue in model group was severely damaged,retention time in target quad-rant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased significantly(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased significantly(P<0.05).Compared with model group,synaptic morphological damage of ischemic peripheral brain tissue in rats in low dose Yiqi Shengqing Formula group and high dose Yiqi Shengqing Formula group was alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were decreased(P<0.05).Compared with low dose Yiqi Shengqing Formula group,damage of synaptic morphology in ischemic peripheral brain tissue of rats in high dose Yiqi Shengqing Formula group was further alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were further increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were further reduced(P<0.05).Compared with high dose Yiqi Shengqing Formula group,synaptic morphological damage of ischemic peripheral brain tissue in high dose Yiqi Shengqing Formula+BDNF knockdown group was aggravated,retention time in target quadrant,times of crossing the platform,number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased(P<0.05);there was no significant changes in each index of rats in high dose Yiqi Shengqing Formula+empty load group(P>0.05).Conclusion:Yiqi Shengqing Formula can inhibit the neuroinflammation of IS rats by activating BDNF-ERK-CREB signal,thereby reducing the damage of its neurons and improving its neural function.

Objective:To evaluate the role of microglial hypoxia-inducible factor-3α (HIF-3α) in cognitive impairment after hemorrhagic shock and resuscitation(HSR) and the relationship with neuronal ferroptosis in mice.Methods:Twenty-four specific pathogen-free healthy male C57BL/6 mice, aged 10 weeks, weighing 25-30 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (Sham group), HSR group, and HSR+ ferroptosis inhibitor (ferrostatin-1) group (HSR+ Fer-1 group). Sixteen C57BL/6 mice and 16 HIF-3α flox/flox: Cx3crl Cre (HIF-3α CKO) mice were selected and assigned to 2 groups ( n=8 each) using a random number table method: sham operation group (WT-Sham group, HIF-3α CKO-Sham group) and HSR group (WT-HSR group, HIF-3α CKO-HSR group). To establish the HSR model, 40% of the total blood volume was withdrawn at a steady rate via the right carotid artery within 30 min and 1 h later reinfused through the jugular vein over a period of 30 min. Ferrostatin-1 10 mg/kg was nasally administered once mice recovered after HSR in HSR+ Fer-1 group. The cognitive function was evaluated by the novel object recognition test at 72 h after developing the model. The hippocampal tissues were collected under deep anesthesia after evaluation for determination of the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) in the ipsilateral hippocampi (by Western blot) and expression of microglial HIF-3α and GPX4 and FTH1 in neurons in the hippocampal CA3 region (by immunofluorescence staining) and for examination of the ultrastructure of mitochondria in hippocampal neurons (with a transmission electron microscope). Results:Compared to Sham group, the cognitive and discrimination indexes were significantly decreased, and the expression of GPX4 and FTH1 was down-regulated in HSR group ( P<0.05). Compared to HSR group, the cognitive and discrimination indexes were significantly increased, and the expression of GPX4 and FTH1 in the hippocampi was up-regulated in HSR+ Fer-1 group ( P<0.05). Compared to WT-Sham group, the cognitive and discrimination indexes were significantly decreased, and the expression of microglial HIF-3α in the hippocampal CA3 region was up-regulated, and the expression of neuronal GPX4 and FTH1 was down-regulated in WT-HSR group ( P<0.05), and no statistically significant change was found in the aforementioned parameters in HIF-3α CKO-Sham group ( P>0.05). Compared to WT-HSR group, the cognitive and discrimination indexes were significantly increased, and the expression of microglial HIF-3α in the hippocampal CA3 region was down-regulated, the expression of GPX4 and FTH1 was up-regulated ( P<0.05), and mitochondrial damage in the neurons was significantly attenuated in HIF-3α CKO-HSR group. Conclusions:Microglial HIF-3α-mediated ferroptosis in hippocampal neurons is involved in cognitive impairment following HSR in mice.

Objective:To investigate the effect of Yiqi Shengqing Formula on neuronal damage in ischemic stroke(IS)rats by regulating brain-derived neurotrophic factor(BDNF)-extracellular regulated protein kinase(ERK)-cyclic adenosine monophosphate-responsive element binding protein(CREB)signal pathway.Methods:IS rat model was prepared by modified thread suppository method,and randomly divided into model group,low dose Yiqi Shengqing Formula(3 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)+empty load group,high dose Yiqi Shengqing Formula(6 g/kg)+BDNF knockdown group,with 10 rats in each group,another 10 healthy rats were set as sham operation group.After intervention with Yiqi Shengqing Formula and plasmid,neural function of rats in each group was scored with Longa scoring method;Morris water maze test was used to detect cognitive impairment of rats in each group;Nissl staining was used to detect the number of neurons in ischemic peripheral brain tissue and hippocampus of rats in each group;synaptic morphology of ischemic peripheral brain tissue was detected by silver staining;levels of TNF-α and IL-8 in brain tissue and serum of rats in each group were measured by ELISA;expressions of BDNF-ERK-CREB signal pathway related proteins in rat brain were detected by Western blot.Results:Compared with sham operation group,synaptic morphology of ischemic peripheral brain tissue in model group was severely damaged,retention time in target quad-rant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased significantly(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased significantly(P<0.05).Compared with model group,synaptic morphological damage of ischemic peripheral brain tissue in rats in low dose Yiqi Shengqing Formula group and high dose Yiqi Shengqing Formula group was alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were decreased(P<0.05).Compared with low dose Yiqi Shengqing Formula group,damage of synaptic morphology in ischemic peripheral brain tissue of rats in high dose Yiqi Shengqing Formula group was further alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were further increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were further reduced(P<0.05).Compared with high dose Yiqi Shengqing Formula group,synaptic morphological damage of ischemic peripheral brain tissue in high dose Yiqi Shengqing Formula+BDNF knockdown group was aggravated,retention time in target quadrant,times of crossing the platform,number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased(P<0.05);there was no significant changes in each index of rats in high dose Yiqi Shengqing Formula+empty load group(P>0.05).Conclusion:Yiqi Shengqing Formula can inhibit the neuroinflammation of IS rats by activating BDNF-ERK-CREB signal,thereby reducing the damage of its neurons and improving its neural function.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective:To evaluate the role of microglial hypoxia-inducible factor-3α (HIF-3α) in cognitive impairment after hemorrhagic shock and resuscitation(HSR) and the relationship with neuronal ferroptosis in mice.Methods:Twenty-four specific pathogen-free healthy male C57BL/6 mice, aged 10 weeks, weighing 25-30 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (Sham group), HSR group, and HSR+ ferroptosis inhibitor (ferrostatin-1) group (HSR+ Fer-1 group). Sixteen C57BL/6 mice and 16 HIF-3α flox/flox: Cx3crl Cre (HIF-3α CKO) mice were selected and assigned to 2 groups ( n=8 each) using a random number table method: sham operation group (WT-Sham group, HIF-3α CKO-Sham group) and HSR group (WT-HSR group, HIF-3α CKO-HSR group). To establish the HSR model, 40% of the total blood volume was withdrawn at a steady rate via the right carotid artery within 30 min and 1 h later reinfused through the jugular vein over a period of 30 min. Ferrostatin-1 10 mg/kg was nasally administered once mice recovered after HSR in HSR+ Fer-1 group. The cognitive function was evaluated by the novel object recognition test at 72 h after developing the model. The hippocampal tissues were collected under deep anesthesia after evaluation for determination of the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) in the ipsilateral hippocampi (by Western blot) and expression of microglial HIF-3α and GPX4 and FTH1 in neurons in the hippocampal CA3 region (by immunofluorescence staining) and for examination of the ultrastructure of mitochondria in hippocampal neurons (with a transmission electron microscope). Results:Compared to Sham group, the cognitive and discrimination indexes were significantly decreased, and the expression of GPX4 and FTH1 was down-regulated in HSR group ( P<0.05). Compared to HSR group, the cognitive and discrimination indexes were significantly increased, and the expression of GPX4 and FTH1 in the hippocampi was up-regulated in HSR+ Fer-1 group ( P<0.05). Compared to WT-Sham group, the cognitive and discrimination indexes were significantly decreased, and the expression of microglial HIF-3α in the hippocampal CA3 region was up-regulated, and the expression of neuronal GPX4 and FTH1 was down-regulated in WT-HSR group ( P<0.05), and no statistically significant change was found in the aforementioned parameters in HIF-3α CKO-Sham group ( P>0.05). Compared to WT-HSR group, the cognitive and discrimination indexes were significantly increased, and the expression of microglial HIF-3α in the hippocampal CA3 region was down-regulated, the expression of GPX4 and FTH1 was up-regulated ( P<0.05), and mitochondrial damage in the neurons was significantly attenuated in HIF-3α CKO-HSR group. Conclusions:Microglial HIF-3α-mediated ferroptosis in hippocampal neurons is involved in cognitive impairment following HSR in mice.

[Objective]To summarize the characteristics and experience of Professor ZHANG Deying in treating acne from the perspective of phlegm syndrome.[Methods]By following the clinical study of Professor ZHANG's clinic,the medical records of acne treatment were sorted out,three typical cases were selected,and combined with the classical theories of traditional Chinese medicine,the unique insights and clinical experience of Professor ZHANG on phlegm syndrome theory were analyzed and summarized.[Results]According to the physical condition of people and the characteristics of acne,Professor ZHANG points out that the etiology and pathogenesis of acne are phlegm heat or phlegm fire invading the head,chest and causing local flesh rot.According to the spleen and stomach of middle-Jiao,the phlegm is a pathogenic factor of soil.In the treatment,the purpose of reducing phlegm can be achieved by reducing soil,multiplying wood to reduce soil and producing metal to eliminate soil,and then using heat-clearing drugs to clear the evil of upper-Jiao phlegm heat and cure acne.At the same time,it should be noted the relationship among the five elements,the phlegm is too excessive,easy to block the kidney water and cause kidney deficiency,the first treatment is reducing phlegm,after the removal of phlegm,tonifying the kidney can be effective,even some patients do not need to be tonified the kidney,and the kidney will slowly recover.[Conclusion]Professor ZHANG has unique understanding of the theory of phlegm syndrome,pointing out that the pathogenesis of acne is mostly phlegm fire or phlegm heat stagnation in the muscle surface,and the flesh rot.The main treatment should be to clear phlegm heat.Phlegm is the pathogenic factor of soil.Besides the method of reducing soil,according to the theory of five elements,there are also methods of multiplying wood to reduce soil and producing metal to eliminate soil.

Objective To establish a mice model of atopic dermatitis with acute itching and investigate the antipruritic effect and its mechanism of Xiaofeng Zhiyang granules(XFZYG).Methods A mice model of atopic dermatitis was prepared by induction method.Mice were sensitized by calcipotriol and ovalbumin(OVA)applying to the right ear daily for 10 days,and then stimulated by OVA injected intradermally into the right cheek to resulting in acute itching.These mice were divided into 5 groups:blank control group,model group,low dose(7.2 g/kg)and high dose(14.4 g/kg)of XFZYG,and positive control group(montelukast 5 mg/kg).Drugs were administered by gavage at 12 h and 30 min before stimulation.The leukotriene levels in the serum of the mice were measured by Elisa and the basophil ratio and activation status in the blood were measured by flow cytometry.Results The mean number of scratches in the model group was 56 between 30 min and 60 min after stimulation,while the mean number of scratches in the low and high dose of XFZYG groups were 42 and 23 respectively,which were significantly lower than those in the model group(P<0.05).The serum leukotriene levels and the proportion of basophils in the low and high dose of XFZYG groups were significantly lower than those in the model group(P<0.05).Conclusion XFZYG had certain therapeutic effect on acute itching of atopic dermatitis in mice,and the mechanism of its action was related to the reduction of leukotriene level and basophil ratio in serum of mice with atopic dermatitis.

Objective:To investigate the expression and role of DEAD-box RNA helicases 5(DDX5 helicases)in head and neck squamous carcinoma(HNSCC).Methods:Tissue microarray microarray was used to assess relevant mRNA expression profile data,and R software was used to screen differential mRNAs(DEGs).The expression level of DDX5 was predicted using GEPIA 2,TCGA databases,and detected by immunohistochemistry,western blot and RT-qPCR in the HNSCC tissue and cell lines.Based on high-throughput sequencing data of DECs,differentially expressed miRNAs(DEMIs)relevant DDX5 competitive endogenous RNA network(ceRNA)was constructed.The software cytoscape was used to visualize the ceRNA network map and further screen the regulatory ax-is.Results:The results of microarray screening revealed that DDX5 expression in HNSCC was upregulated.Immunohistochemistry ver-ified that DDX5 was stronger expressed in the nuclei of squamous carcinoma cells.qPCR results suggested that significant expression of DDX5 mRNA at the tissue and cellular levels(P＜0.05).Western blot results showed high expression of DDX5 protein in the tissues.The ceRNA network was constructed,from which the relevant HNSCC axis circRNA-039626-miR-222-5p-DDX5 was identified.Con-clusion:DDX5 is highly expressed in HNSCC,and the circRNA-039626-miR-222-5p-DDX5 axis may be a potential regulatory axis for the development of HNSCC.

Objective:To explore the clinical characteristics of mirtazapine-related thrombocytopenia.Methods:The diagnosis and treatment of a patient with mirtazapine-related thrombocytopenia who was admitted to the Aerospace Center Hospital was reported, and the main clinical data (gender, age, indications of mirtazapine use, dosage of mirtazapine, combined medication, platelet count before and after medication, time from application of mirtazapine to thrombocytopenia occurrence, clinical treatment and prognosis, etc.) of the case and similar cases collected by searching relevant databases (up to August 31, 2023) were analyzed by descriptive statistic method.Results:A total of 9 patients were enrolled in the analysis, including 4 males and 5 females; the age ranged from 28 to 74 years, with a median age of 52 years. The indication of medication was depression in 8 patients, and 1 had no record. The daily dose of mirtazapine was 15 mg in 4 patients, 30 mg in 3 patients, and no record in 2 patients. Two patients were treated with mirtazapine alone, 6 patients were treated with mirtazapine combined with other drugs, and it was not recorded in 1 patient. The time from the application of mirtazapine to occurrence of thrombocytopenia in the 9 patients ranged from 2 to 28 days, with a median time of 8 days. The severity of thrombocytopenia was grade 1, 3, and 4 in 3, 3, and 2 patients, respectively; 1 patient had no relevant record. Of the 5 patients with severe thrombocytopenia, 3 developed bleeding, and 1 had skin ecchymosis. The results of drug-dependent antiplatelet antibody test in 2 patients were positive. Nine patients stopped mirtazapine treatment after diagnosis of thrombocytopenia, 6 patients did not receive special intervention, and 3 patients were given symptomatic treatments. After drug withdrawal for 2-43 days with the median time of 9 days, platelet counts returned to the reference range in 7 patients, platelet count increased in 1 patient, and platelet count was unknown but skin symptom was improved in 1 patient.Conclusions:Mirtazapine-related thrombocytopenia usually occurs within 10 days of treatments, which can be improved after drug withdrawal. It is suggested to monitor the blood routine before and after the application of mirtazapine.

Objective:To explore the clinical characteristics of mirtazapine-related thrombocytopenia.Methods:The diagnosis and treatment of a patient with mirtazapine-related thrombocytopenia who was admitted to the Aerospace Center Hospital was reported, and the main clinical data (gender, age, indications of mirtazapine use, dosage of mirtazapine, combined medication, platelet count before and after medication, time from application of mirtazapine to thrombocytopenia occurrence, clinical treatment and prognosis, etc.) of the case and similar cases collected by searching relevant databases (up to August 31, 2023) were analyzed by descriptive statistic method.Results:A total of 9 patients were enrolled in the analysis, including 4 males and 5 females; the age ranged from 28 to 74 years, with a median age of 52 years. The indication of medication was depression in 8 patients, and 1 had no record. The daily dose of mirtazapine was 15 mg in 4 patients, 30 mg in 3 patients, and no record in 2 patients. Two patients were treated with mirtazapine alone, 6 patients were treated with mirtazapine combined with other drugs, and it was not recorded in 1 patient. The time from the application of mirtazapine to occurrence of thrombocytopenia in the 9 patients ranged from 2 to 28 days, with a median time of 8 days. The severity of thrombocytopenia was grade 1, 3, and 4 in 3, 3, and 2 patients, respectively; 1 patient had no relevant record. Of the 5 patients with severe thrombocytopenia, 3 developed bleeding, and 1 had skin ecchymosis. The results of drug-dependent antiplatelet antibody test in 2 patients were positive. Nine patients stopped mirtazapine treatment after diagnosis of thrombocytopenia, 6 patients did not receive special intervention, and 3 patients were given symptomatic treatments. After drug withdrawal for 2-43 days with the median time of 9 days, platelet counts returned to the reference range in 7 patients, platelet count increased in 1 patient, and platelet count was unknown but skin symptom was improved in 1 patient.Conclusions:Mirtazapine-related thrombocytopenia usually occurs within 10 days of treatments, which can be improved after drug withdrawal. It is suggested to monitor the blood routine before and after the application of mirtazapine.