To analyze the epidemiological characteristics of acute respiratory infections (ARIs) during the autumn-winter season in Beijing, providing evidence for the prevention, control, diagnosis, and treatment of ARIs.

Objective To explore the mechanism of Xinkang Prescription (Descurainiae Semen Lepidii Semen,Armeniacae Semen Amarum,Poria,Astragali Radix,Citri Reticulatae Pericarpium,Sparanii Rhizoma) for purging the lung and promoting diuresis in treating heart failure by regulating phosphorylation of phospholamban (PLN). Methods Forty-eight C57BL/6J mice were randomly divided into sham-operation group,model group,low-,medium-and high-dose Xinkang Prescription groups(0.455,0.91,1.82 g·kg-1),as well as Entresto group (25 mg·kg-1),with eight mice in each group. The model of ischemic heart failure was established by ligating the left anterior descending coronary artery in mice. After the model was successfully replicated,mice were orally administered with the above-mentioned dosages of Xinkang Prescription and Entresto once a day for four weeks,while sham-operation group and model group were given 0.9％ sodium chloride solution by gavage at the same time. Echocardiography was used to detect the cardiac function of the mice in each group,including left ventricular ejection fraction (LVEF),left ventricular fractional shortening (LVFS),left ventricular end-diastolic dimension (LVEDD) and left ventricular end systolic diameter (LVESD). Hematoxylin-eosin (HE) staining was used to observe the pathological changes in cardiac tissue of mice. qRT-PCR was used to detect the mRNA expression of BNP. Western Blot and Jess were used to detect the expression of PLN,p-Thr17-PLN,p-Ser16-PLN,sarcoplasmic reticulum calcium ATPase 2a (SERCA2a),protein kinase A (PKA),p-PKA,Ca2+/calmodulin-dependent kinaseⅡ(CaMKⅡ) and p-CaMKⅡ in cardiac tissue,and to calculate the ratio of SERCA2a/PLN. The SERCA2a activity was determined by the inorganic phosphorus method.Results Compared with the sham-operation group,the model group showed a significant decrease in LVEF and LVFS(P<0.01) and a significant increase in LVEDD and LVESD (P<0.01). HE staining showed the fibril of cardiac muscle broke and disarranged,accompanied by inflammatory cell infiltration. The mRNA expression of BNP was significantly up-regulated (P<0.01),and the protein expressions of p-Ser16-PLN,p-Thr17-PLN,p-PKA,the ratio of SERCA2a/PLN and SERCA2a activity were significantly down-regulated (P<0.01),while the expression of p-CaMKⅡ was up-regulated (P<0.01). Compared with the model group,LVEF and LVFS in medium-,high-dose Xinkang Prescription groups were significantly increased(P<0.01),while LVEDD and LVESD were significantly decreased (P<0.01). HE staining showed significant improvement in the pathological damage of cardiac tissue. The expression level of BNP was significantly decreased (P<0.01),while the protein expressions of p-Ser16-PLN,p-Thr17-PLN,p-PKA,the ratio of SERCA2a/PLN and SERCA2a activity were significantly increased (P<0.01). The protein expression of p-CaMKⅡ was remarkably decreased(P<0.05). Conclusion Xinkang Prescription can effectively improve cardiac function of mice with heart failure,which may be related to enhance phosphorylation levels of phospholamban.

Objective To investigate the mechanism of Guizhi Tongluo Tablets(GZTLP)on improving atherosclerosis in APOE knockout mice by regulating neutrophil extracellular trapping nets(NETs).Methods After modeling,24 APOE knockout mice aged 8 weeks were randomly divided into 4 groups:GZTLP high-dose group,low-dose group,model control group and normal control group,with 6 mice in each group.GZTLP was given 1.87 mg·g-1 and 0.47 mg·g-1 intragastric administration in high-dose group and low-dose group,respectively.The normal control group and model control group were given 0.9%sodium chloride solution intragastric administration for 6 weeks,and the lipid plaque deposition in aorta was observed by gross oil red O staining.Lipid deposition in aortic root was observed by oil red O staining.The pathological changes of lipid plaques in aortic root were observed by HE staining.The levels of interleukin-1β(IL-1β)and tumor necrosis factor α(TNF-α)in peripheral blood of mice were detected by enzyme-linked immunosorbent assay(ELISA).The expression of lymphocyte antigen 6G(Ly6G),myeloperoxidase(MPO)and citrulinated histone(Cit-H3)in plaques of the aortic arch and the colocalization of Ly6G,MPO and Cit-H3 were detected by immunofluorescence assay.Results Compared with the normal control group,the aorta of mice in the model control group showed serious lipid plaque deposition,morphological damage,and a large number of inflammatory cells infiltration,the contents of serum inflammatory factors IL-1β and TNF-α were increased,and the protein expressions of Ly6G,Cit-H3 and MPO were significantly increased.Compared with model control group,GZTLP group reduced the amount of lipid plaque deposition in aorta,the arrangement of aortic cells was more regular,the inflammatory cell infiltration was improved,and the contents of serum inflammatory factors IL-1β and TNF-α were significantly decreased(P<0.05).The colocalization and the protein expression of Ly6G,MPO and Cit-H3 were significantly decreased in aortic tissues(P<0.01).Conclusions GZTLP can improve atherosclerosis,and its mechanism may be related to the inhibition of neutrophil extracellular trapping nets.

BACKGROUND:Reconstruction of the medial patellofemoral ligament is the primary and basic treatment for patellofemoral dislocation.Generally,autologous or allogeneic tendons are used to fix the patellofemoral podogram area and the femoral insertion,respectively.There are various fixation methods.Patellar lateral insertion fixation methods are relatively diverse,mainly traditional transosseous fixation and recent anchoring methods,including single tunnel,double-tunnel transosseous fixation,and two-wire anchor fixation.However,which fixation method is more effective in reducing patellofemoral joint stress and is more biomechanical has not been determined. OBJECTIVE:To observe the mechanical effects of patellofemoral joint and medial patellofemoral ligament reconstruction with transosseous and wire anchor fixation. METHODS:A three-dimensional finite element model of the knee joint was constructed.The medial patellofemoral ligament was reconstructed by a single tunnel through the bony canal or two wire anchors at the medial edge of the patella.The femoral side was fixed by extrusion nails to the medial epicondyle of the femur and the midpoint of the adductor tubercle.We observed the effects of the two fixation methods on patellofemoral joint and medial patellofemoral ligament loading during knee flexion at 0°,30°,60°,90°,and 120°. RESULTS AND CONCLUSION:(1)The stress on the patellofemoral joint was large when the knee was at flexion of 0-60°,peaked at 30°,and gradually decreased at 90° and 120°.The two fixation methods had little difference in the stress on the patellofemoral joint.(2)The stress on the medial patellofemoral ligament peaked at 30° and decreased significantly at 60°,and the load on the medial patellofemoral ligament was significantly greater at all angles with anchor fixation than with bony canal fixation.(3)The results showed that there was no significant difference in patellofemoral joint loading between the two fixation methods,but the stress on the medial patellofemoral ligament in anchoring was significantly greater than that in transosseous fixation.

Objective:To analyze the clinical and laboratory characteristics of acute myeloid leukemia (AML) patients with NPM1 mutation, and to explore the prognostic factors.Methods:A total of 77 AML patients with NPM1 gene mutation admitted to Hebei Yanda Ludaopei Hospital from May 1st 2012 to December 31st 2021 were enrolled in the study, including 34 male and 43 female patients. The median age was 40 (3, 68) years old. Patients were selected and divided into 4 groups according to the morphological FAB classification. There were 29 cases (37.7%) of M1 type, 13 cases (16.9%) of M2 type, 23 cases (29.9%) of M4 type, and 12 cases (15.5%) of M5 type. The clinical characteristics, bone marrow/peripheral blood cell morphology, immunophenotype, cytogenetics, molecular biology and overall survival of different groups were retrospectively analyzed, and the risk factors affecting the prognosis of AML were also explored. Cox multivariate regression was used to analyze the clinical influencing factors of survival and prognosis.Results:The white blood cell counts were highest in M4 and M5 patients and lowest in M2 patients, while no significant difference in the red blood cell, hemoglobin, and platelet counts( P>0.05). Morphologically, there were significant differences in the percentage of blasts and blasts with cup-like nuclei on bone marrow (BM) and peripheral blood (PB). The proportion of blasts in BM and PB was the highest in M1 and the lowest in M2 ( P<0.001). The positive rate of blasts with cup-like nuclei was the highest in M1 and the lowest in M5 of BM ( P<0.001), while the highest in M2 and the lowest in M5 of PB ( P=0.006). The scores of myeloperoxidase and chloroacetate esterase were all the highest in M1 and the lowest in M5 ( P<0.001, 0.001, respectively). In terms of molecular biology, the occurence rate of blasts combined with DNMT3A mutation was the highest in M4 and the lowest in M2 ( P=0.044), while those combined with FLT3-ITD mutation was the highest in M4 and the lowest in M5 ( P=0.002). In immunophenotype, there were significant differences in the expression positivities of seven antigens including HLA-DR, CD56, CD11c, CD15, CD14, CD96 and cMPO ( P<0.05). Multivariate COX regression analysis showed that no recurrence after treatment ( P<0.001), complete remission after treatment ( P=0.015) and transplantation ( P<0.001) were correlated with overall survival (OS). No recurrence after treatment ( P=0.033), transplantation ( P=0.027), no mutation of FLT3-ITD ( P=0.040), and hemoglobin concentration ( P=0.023) were associated with relapse-free survival (RFS). Survival analysis by Kaplan-Meier curve showed that there was no significant difference in survival time between the M1, M2, M4 and M5 groups in OS and RFS. Conclusion:There were significant differences in the white blood count, the percentage of blasts and blasts with cup-like nuclear morphology, cytochemical staining (MPO integration, CE integration and percentage of NAS-DCE), gene mutation (DNMT3A and FLT3-ITD) and immunophenotypes (HLA-DR, CD56, CD11c, CD15, CD14, CD96 and cMPO) between the four groups. The multivariate analysis revealed that no recurrence after treatment and transplantation were independent prognostic factors in NPM1 mut AML patients. On the other hand, FLT3-ITD mutation and hemoglobin concentration were associated with RFS and complete remission after treatment was associated with OS in the entire NPM1 mut cohort.

OBJECTIVE: To analyze variants of SMN gene in a Chinese pedigree affected with Spinal muscular atrophy (SMA). METHODS: A Chinese pedigree diagnosed at the Nanchang First Hospital in January 2020 was selected as the study subject. Peripheral blood samples were collected for the extraction of DNA. All exons of the SMN gene were detected by multiple ligation-dependent probe amplification (MLPA). Potential variants of the SMN gene were also detected by Whole exome sequencing (WES), and the result was verified by Sanger sequencing. cDNA extracted from fresh blood sample was used as a template to verify the location of variant on the SMN genes. RESULTS: The proband was found to harbor a heterozygous deletion of the SMN1 Exon7+Exon8, and a heterozygous c.81G>A variant. The SMN1 Exon7+Exon8 deletion was inherited from her father and grandmother, whilst the c.81G>A variant was inherited from her mother and maternal grandfather. Her aunt was also a carrier of the heterozygous deletion, while her paternal aunt, her husband, and their daughter were not. cDNA amplification and Sanger sequencing confirmed that the c.81G>A variant was located in the SMN1 gene. CONCLUSION MLPA combined with NGS and Sanger sequencing can identify compound heterozygous variants of the SMN gene in the SMA patients.
Female ; Humans ; Male ; DNA, Complementary ; East Asian People ; Fathers ; Mothers ; Muscular Atrophy, Spinal/diagnosis* ; Pedigree ; Survival of Motor Neuron 1 Protein/genetics*

Objective To prepare propranolol hydrochloride loaded cubosomes (PPL-Cubs) with high entrapment efficiency. Methods PPL-Cubs was prepared by pH gradient method. Pressure and cycles of high pressure homogenization, dosage of glyceryl monooleate and poloxamer 407 were optimized to prepare blank cubosomes with particle size and polydispersity index as the indexes. The influences of various factors, including exterior pH values, internal pH values, the ratio of carrier to drug, particle size and polydispersity index of blank cubosomes, incubation temperature and time, and drug concentration on the entrapment efficiency were investigated. Results The blank cubosomes with small particle size and polydispersity index was prepared under homogenization conditions of 900 bar for 7 cycles, glyceryl monooleate dosage of 25%, and poloxamer 407 dosage of 5%. PPL-Cubs showed high entrapment efficiency with exterior pH value of 8.5, internal pH value of 3.0, ratio of carrier to drug of 6∶1, incubation temperature of 20 ℃, and incubation time of 15 min, and drug concentration of 1%. The particle size and polydispersity index of blank cubosomes showed no influence on entrapment efficiency. Conclusion PPL-Cubs with high entrapment efficiency could be prepared under the pH gradient method.

Objective:To investigate the relationship between the expression of hepatocyte nuclear factor-1 α (HNF-1α) and the occurrence and development of liver inflammation and fibrosis in liver tissues of patients with chronic hepatitis B.Methods:Sixty-four patients with chronic hepatitis B who were diagnosed and treated in our hospital from 2011 to 2018 were selected. All patients underwent ultrasound-guided aspiration liver biopsy. The pathological results of liver biopsy were collected for inflammation grading and fibrosis staging. The liver puncture biopsies was collected by paraffin sectioning. The expression of HNF1α in the liver tissue was detected by immunohistochemical staining. Mantel-Haenszel χ2 test was used for bidirectional ordered grouping data, and Spearman’s rank-correlation test was used for rank correlation analysis. Results:There were varying degrees of inflammatory necrosis and fibrosis in the liver tissues of patients with chronic hepatitis B. There was a linear relationship between the expression of HNF1α and the level of inflammation in liver tissues ( χ2MH = 40.70, P < 0.05). The expression of HNF1α in liver tissues of patients with chronic hepatitis B was decreased with the increase of liver inflammation. The expression intensity of HNF1α was negatively correlated with the inflammation grade ( rs = -0.815, P < 0.05). There was a linear relationship between the expressions of HNF1α and the degree and stage of liver fibrosis ( χ2MH = 31.95, P < 0.05). The expression level of HNF1α in liver tissue was gradually decreased with the aggravation of liver fibrosis. The expression intensity of HNF1α was negatively correlated with fibrosis stage ( rs = -0.713, P < 0.05). Conclusion:HNF1α is closely related to the occurrence and development of liver tissue inflammation and fibrosis, and is expected to be a sensitive indicator for evaluating the level of liver tissue inflammation and fibrosis in patients with chronic hepatitis B. In addition, its down-regulation may be involved in the process of occurrence and development of liver inflammation and liver fibrosis, and may become a new target for the treatment of chronic hepatitis B.

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.

Objective:To compare the curative effect of hematoma removal and minimally invasive puncture drainage in hypertensive intracerebral hemorrhage (HICH) under neuroendoscope.Methods:The clinical data of 118 patients with HICH admitted to our hospital from February 2017 to November 2019 were retrospectively analyzed. According to the different surgical methods, the patients were divided into group A ( n=59, minimally invasive puncture and drainage) and group B ( n=59, neuroendoscopic hematoma removal). The perioperative indexes, complications and neurological function indexes [neuron specific enolase (NSE), neurotrophic factor (NGF), substance P (SP)], inflammatory factor index [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)] and related scale scores [National Institutes of Health Stroke Scale (NIHSS), modified Barthel Index (mBI)] were compared between the two groups. Results:The operation time, cerebrospinal fluid recovery time, hematoma removal time and hospitalization time of group B were shorter than those of group A ( P<0.05). On the 7th day after operation, the NSE, SP, IL-6, TNF-α in the two groups were decreased, and the levels of NSE, SP, IL-6 and TNF-α in group B were lower than those in group A ( P<0.05); on the 7th day after operation, the levels of NGF in two groups were increased, and those in group B were higher than those in group A ( P<0.05). 6 months after operation, the NIHSS decreased and mBI increased in both groups ( P<0.05), and NIHSS in group B was lower than that in group A, but mBI was higher than that in group A ( P<0.05). There was no difference in the incidence of complications between the two groups ( P>0.05). Conclusions:Compared with minimally invasive puncture and drainage, neuroendoscope hematoma removal for HICH patients can effectively improve perioperative indicators, reduce neurological damage and body inflammatory stimulation, and improve the self-care ability of patients, which is safe and reliable.