BACKGROUND:Kidney deficiency is the main pathogenesis of osteoporosis.To study the relationship between the two major syndrome types of kidney deficiency,Kidney-Yang deficiency and Kidney-Yin deficiency,is beneficial for the development of clinical diagnosis and treatments based on the combination of disease and syndrome. OBJECTIVE:To evaluate the biomechanical differences of the rat femurs with Kidney-Yang deficiency and Kidney-Yin deficiency caused by Yougui pills,and to demonstrate the scientific efficacy of medication based on the combination of disease and syndrome in osteoporosis from a biomechanical perspective. METHODS:The bilateral ovaries of 60 female Sprague-Dawley rats were surgically removed to establish an ovariectomized osteoporosis model.At 10 weeks after modeling,all the rats were randomly divided into a Kidney-Yang deficiency group(n=30)and a Kidney-Yin deficiency group(n=30).Rats with Kidney-Yang deficiency were given gluteal intramuscular injection of hydrocortisone,while rats with Kidney-Yin deficiency were orally administered with thyroid tablet suspension,once a day,for 14 consecutive days.After successful modeling,20 rats in each group were given a suspension of Yougui pills by gavage once a day for 12 consecutive weeks and the remaining 10 rats were used as the control group without intervention.After gavage,the microstructural parameters of the bone were measured using Micro-CT scanning.Three-point bending,finite element simulation,femoral head compression,and surface indentation distribution experiments of the femurs were performed on a mechanical testing machine. RESULTS AND CONCLUSION:Micro-CT revealed that the femoral bone density,bone volume fraction,bone surface density,trabecular number,and trabecular separation were improved in the Kidney-Yin deficiency+Yougui pills group compared with the Kidney-Yin deficiency group(P＜0.05);the femoral bone volume fraction,bone surface density,trabecular number,and trabecular thickness were improved in the Kidney-Yang deficiency+Yougui pills group compared with the Kidney-Yang deficiency group(P＜0.05).The three-point bending experiment showed that the femur elastic modulus,maximum bending strength and bending fracture strength were decreased(P＜0.05)and toughness was increased(P＜0.05)in the Kidney-Yang deficiency+Yougui pills group compared with the Kidney-Yang deficiency group.Finite element simulation showed that Yougui pills could significantly improve the bending resistance of the femurs in the Kidney-Yang deficiency group,but had no significant effect on the Kidney-Yin deficiency group.The femoral head compression experiments showed that Yougui pills could enhance the ability of the femoral head to resist deformation in the Kidney-Yang deficiency group,but there was no significant difference in the effect of Yougui pills on the surface properties of the femoral head in the Kidney-Yin deficiency group and the Kidney-Yang deficiency group.To conclude,Yougui pills can significantly enhance the biomechanical properties of the osteoporotic bones with Kidney-Yang deficiency,but have no significant effect on the osteoporotic bone with Kidney-Yin deficiency.

Objective To investigate the effects of modified Yupingfeng Powder medicated serum on the inflammatory response of rat lung epithelial type Ⅱ cells RLE-6TN;To explore the mechanism based on nuclear factor(NF)-κB signaling pathway.Methods The inflammatory reaction of RLE-6TN cells was induced by lipopolysaccharide,and the cells were divided into control group,model group,dexamethasone medicated serum group,and 5%,10%and 20%TCM serum group,and the cell model was intervened with different serum.After 24 hours,the content of lactate dehydrogenase(LDH)in cell supernatant was detected by kit,and the content of reactive oxygen species(ROS)in cells were detected by fluorescence staining,Hoechst/PI double staining was used to observe cell apoptosis,and ELISA was used to detect tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1β contents in cell supernatant,RT-qPCR was used to detect Toll like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and NF-κB inhibitory protein α(IκBα)mRNA expression,Western blot was used to detect protein expressions of TLR4,MyD88,NF-κBp65 and IκBα.Results Compared with the control group,the contents of LDH,TNF-α,IL-6,IL-1β in RLE-6TN cell supernatant and ROS content in cells of model group significantly increased(P<0.01),the cell apoptosis rate significantly increased(P<0.01),the expressions of TLR4 and MyD88 mRNA and protein significantly increased(P<0.01),the expression of IκBα mRNA significantly decreased(P<0.01),and the ratio of p-NF-κBp65/NF-κBp65 and p-IκBα/IκBα significantly increased(P<0.01).Compared with the model group,the content of LDH,TNF-α,IL-6,IL-1 in RLE-6TN cell supernatant and ROS content in cells significant decreased in the 20%TCM serum group and dexamethasone medicated serum group(P<0.01),the cell apoptosis rate significantly decreased(P<0.01),the expressions of TLR4 and MyD88 mRNA and protein significantly decreased(P<0.05,P<0.01),the expression of IκBα mRNA significantly increased(P<0.01),and the ratio of p-NF-κBp65/NF-κBp65 and p-IκBα/IκBα significantly decreased(P<0.05,P<0.01).Conclusion Modified Yupingfeng Powder medicated serum can reduce RLE-6TN cells inflammatory reaction,and its mechanism may be related to the regulation of NF-κB signaling pathway.

Abstract: Objective To analyze the changes in the pathogen spectrum of severe lower respiratory tract viral infections in children before and during the outbreak of the COVID-19 pandemic, and to explore the epidemiological characteristics to provide a basis for preventing respiratory viral infections. Methods We conducted a retrospective analysis of clinical data from patients with severe viral pneumonia admitted to the pediatric intensive care unit (PICU) of Shenzhen Children's Hospital from January 2017 to December 2021. Taking the outbreak of the COVID-19 pandemic as the cut-off point, it is separated into the period before the outbreak of the COVID-19 pandemic and the period during the pandemic. Virus spectrum and clinical data between the two groups were analyzed using the chi-square test or Fisher's exact probability method. Results A total of 712 cases of severe viral pneumonia were reported, including 469 males and 243 females, with a median age of 1.25 (0.50, 3.83) years. Among them, 495 cases were under 3 years old, and 626 cases were under 6 years old. The median duration of illness before admission to the PICU was 3.00 (2.00, 5.00) days. Hospital-acquired infections were seen in 6.88% of the children. Firty-four children had been hospitalized ≥2 times due to repeated infections. The detected viruses were influenza viruses (IVA and IVB) in 223 cases (160 IVA and 70 IVB), respiratory syncytial virus (RSV) in 215 cases, human rhinovirus (HRV) in 125 cases, adenovirus (ADV) in 91 cases, human parainfluenza viruses (HPIV) in 53 cases, human bocavirus (HBoV) in 34 cases, cytomegalovirus (CMV) in 26 cases, human metapneumovirus (HMPV) in 17 cases, and human coronavirus (HCoV) in 7 cases. A total of 634 cases were infected with a single virus, while 78 cases were infected with multiple viruses. The top three viruses, sorted by age, were as follows: <1 year: RSV, IVA/B, and HRV; 1-<3 years: IVA/B, RSV, and ADV; 3-<6 years and 6-<10 years: IVA/B, HRV, and ADV; 10-<14 years: HRV, IVA/B, and CMV; sorted by time distribution: March-May and June-August: RSV, IVA/B, and ADV; September-November: RSV, HRV, and IVA/B; December-February: IVA/B, RSV, and HRV. Before the COVID-19 epidemic, the top three viruses were IVA/B, RSV, and ADV, while during the COVID-19 epidemic were HRV, RSV, and HPIV. Conclusions During the COVID-19 pandemic, the viral spectrum of severe lower respiratory tract viral infections in the PICU changed. Before the pandemic, IVA/B, RSV, and ADV were prevalent, while during the pandemic, HRV, RSV, and HPIV were more prevalent. The viral spectrum varies among children of different age groups and in different months.

Objective: To explore the relationship between maternal emotional symptoms and emotional and behavioral problems (EBPs) of preschool offspring, and to provide reference for prevention and intervention of emotional and behavior problems in preschool children. Methods: A total of 4 100 preschool children aged 3-6 in Fuyang City were enrolled by stratified cluster sampling method in June 2021. The Strengths and Difficulties Questionnaire (SDQ) and Depression Anxiety and Stress Scale (DASS-21) were used to investigate preschool children s EBPs and maternal emotional symptoms, respectively. Results: The detection rates of preschool children s emotional symptoms, conduct problems, hyperactivity, peer interaction problems, prosocial behavior and difficulty scores were 15.7%, 17.4%, 20.0%, 32.3%, 15.1% and 15.8%, respectively. The detection rates of mother s depression, anxiety and stress symptoms were 7.9%, 12.7% and 4.8%, respectively. Multivariate Logistic regression analysis showed that, compared with children of mothers with no depression, anxiety and stress symptoms, offspring of mothers reported depression, anxiety and stress symptoms had significantly higher risks of emotional symptoms, conduct problems, hyperactivity, peer problems and total difficulties ( OR=1.76-6.35, P <0.01). Maternal emotional symptoms had the most significant effect on children s emotional symptoms, and there was no significant correlation between maternal stress symptoms and children s prosocial behavior ( OR=1.40, P >0.05). There was no significant gender difference in the relationship between maternal emotional symptoms and children s emotional and behavioral problems ( ROR=0.73-1.07, P >0.05). For only children whose mothers reported stress symptoms showed a higher risk of emotional and behavior problems than non singleton children ( ROR=2.03, P <0.05). Conclusion Maternal emotional symptoms are related to preschool children s emotional and behavioral problems. Early identification and intervention of mother s negative emotional symptoms, are beneficial to the prevention of preschool children s emotional and behavioral problems.

Objective:To investigate the treatment and prognosis of children with propionic acidemia (PA).Methods:This study involved 82 children with PA treated in the Department of Pediatric Endocrinol-ogy and Genetic Metabolism, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from December 2002 to June 2020. Clinical data, including manifestations, laboratory test results, treatment strategy, and follow-up data, were summarized and analyzed using t-test or Mann-Whitney U test. Results:(1) Among the 82 cases consisting of 50 (61.0%) boys and 32 (39.0%) girls, 59 (72.0%) were diagnosed after clinical onset; 22 (26.8%) were diagnosed by newborn screening, including eight asymptomatic ones; the other one (1.2%) was asymptomatic but confirmed after the diagnosis of PA in the patient's sibling. The average age at first onset was 4.5 months (2 d-5 years) in 73 subjects, of which 28 (38.4%) were early-onset PA (within three months after birth). (2) Cranial MRI was performed on 26 cases, and abnormality was identified in 19 (73.1%) cases. (3) Hyperlactatemia was found in 16 cases among 30(53.3%) who underwent relevant examination with the average lactic acid level of 3.5 (2.1-4.3) μmol/L, while 35 out of 40 patients (87.5%) had hyperammonemia with an average blood ammonia level of 105.4 (34-907) μmol/L. (4) Among the 28 early-onset PA cases, 16 (57.1%) died, and 12 (42.9%) survived. There was no significant difference in the serum propionylcarnitine level, propionylcarnitine to acetylcarnitine ratio, urine 3-hydroxypropionic acid, or methylcitrate level between the survival and death cases. (5) Genetic mutations were detected in 75 patients (91.5%), among which 26 (34.7%) carried PCCA gene mutations and 48 (64%) with PCCB gene mutations. One patient (1.3%) harbored one known pathogenic mutation in each of the PCCA and PCCB genes. All mutations were inherited from the parents. (6) Followed up to June 2020, 57 (69.5%) patients survived, and 25 (30.5%) died from multiple organ failure secondary to severe acidosis, including 16 early-onset and nine late-onset cases. Conclusions:The primary treatment of PA is dietary control. Most PA patients are diagnosed after clinical onset, but symptoms may recur and even have developmental retardation despite treatment. Some of those diagnosed through newborn screening are asymptomatic after treatment. Newborn screening using tandem mass spectrometry is recommended for early diagnosis and treatment of PA.

Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-I-mediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63- or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.
A549 Cells ; Animals ; Apoptosis Regulatory Proteins/immunology* ; DEAD Box Protein 58/immunology* ; Dogs ; HEK293 Cells ; Humans ; Influenza A Virus, H1N1 Subtype/immunology* ; Madin Darby Canine Kidney Cells ; Mice ; Mice, Knockout ; Orthomyxoviridae Infections/pathology* ; Proteolysis ; RAW 264.7 Cells ; Signal Transduction/immunology* ; THP-1 Cells ; TNF Receptor-Associated Factor 3/immunology* ; Ubiquitination/immunology* ; Viral Proteins/immunology*

Objective To investigate the effect of self-made traditional Chinese medicine(TCM) decoction on pregnancy outcome in patients with hypertensive disorder complicating pregnancy. Methods A total of 124 pregnant hypertensive patients admitted to the Department of Critical Care of Guizhou Provincial People's Hospital from October 2016 to October 2018 were enrolled. The 62 patients who were treated with western medicine conventional method;62 patients who were treated with self-made TCM decoction on the basis of western medicine conventional method. The western medicine conventional treatment group was given magnesium sulfate combined with nicardipine; the self-made TCM treatment group was supplemented with TCM decoction on the basis of conventional western medicine treatment (composition: uncaria, raw oyster 20 g, gastrodia elata, eucommia, salvia miltiorrhiza, medlar rehmannia glutinosa each 15 g, rhizoma, mulberry parasitic, astragalus, ophiopogonis each 10 g. Severe headache and dizziness plus tortoise shell, gentian grass 15 g, anemarrhenae 10 g; severe edema plus cassia twig, aristolochiae 15 g, astragali, ginger skin 10 g), be decocted in water for oral dose, morning and evening oral, one dose a day, 1 week for a course of treatment, the two groups were continued for 4 weeks after the evaluation of clinical efficacy. The changes of blood pressure and blood coagulation parameters, placental bed arterial hemodynamics, pregnancy outcome index were observed before and after treatment; antihypertensive effects and adverse reactions after treatment were recorded. Results After treatment, the systolic blood pressure (SBP), diastolic blood pressure (DBP), Fibrinogen (Fib), placental bed arterial pulsation index (PI), end-systolic blood flow velocity and end-diastolic blood flow velocity ratio (S/D) and resistance index (RI) in both groups were lower than those before treatment, the prothrombin time (PT) and activated partial thromboplastin time (APTT) were significantly longer than before treatment, and the time-averaged flow rate (TAV) increased than that before treatment; SBP, DBP, Fib, PI, S/D and RI were significantly lower in self-made TCM treatment group than those in western medicine conventional treatment group [SBP (mmHg, 1 mmHg = 0.133 kPa): 114.26±17.07 vs. 132.72±17.64, DBP (mmHg): 82.98±6.24 vs. 90.09±6.48, Fib (g/L): 3.21±0.45 vs. 3.64±0.31, PI: 0.59±0.14 vs. 0.75±0.15, S/D: 1.70±0.21 vs. 1.93±0.25, RI: 0.43±0.08 vs. 0.54±0.12, all P < 0.05], PT, APTT, TAV in self-made TCM treatment group were significantly higher than western medicine conventional treatment group [PT (s): 12.26±0.57 vs. 11.72±0.44, APTT (s): 27.11±1.34 vs. 25.69±1.48, TAV (cm/s): 15.64±2.88 vs. 12.49±2.76, all P < 0.05]. The rate of cesarean section, postpartum hemorrhage, fetal heart abnormality and neonatal asphyxia in self-made TCM treatment group were significantly lower than those in western medicine conventional treatment group [cesarean section rate: 9.84% (6/61) vs. 27.78% (15/54), postpartum hemorrhage rate: 1.64% (1/61) to 14.81% (8/54), fetal heart abnormal rate: 3.28% (2/61) vs. 16.67% (9/54), the incidence of neonatal asphyxia: 1.64% (1/61) vs. 12.96% (7/54), all P < 0.05]. The total effective rate of the self-made TCM treatment group was significantly higher than that of western medicine conventional treatment group [98.39% (61/62) vs. 87.10% (54/62), P < 0.05]. However, there was no significant difference in the incidence of adverse reactions between the self-made TCM treatment group and western medicine conventional treatment group [16.39% (10/61) vs. 16.67% (9/54), P > 0.05]. Conclusion Self-made TCM decoction can improve the maternal and infant outcomes by improving the hypercoagulable state and placental hemodynamics in hypertensive patients with hyperthyroidism, the antihypertensive effect is remarkable and the safety is good.

Objective To investigate the difference between histopathological changes of brain white matter in low-density lipoprotein receptor (LDLR) homozygous mutation rats with hypercholesterolemia and wild-type rats.Methods Thirty LDLR-/-rats and 28 wild-type rats were selected.Plasma cholesterol levels were measured by enzyme-linked immunosorbent assay at 15,18 and 26 weeks old respectively.The axonal structure of the corpus callosum area was observed by transmission electron microscopy.The myelin basic protein (MBP) of the corpus callosum area was quantitatively analyzed by Western blotting.In addition,at 26 weeks old,the myelin sheaths were stained by fast blue staining.The expression level of MBP in white matter was further detected by immunofluorescence staining,and the morphological changes of glial cells were observed.Results Compared with the wild-type rats,the plasma cholesterol concentration in LDLR-/-rats increased significantly,and it could be as high as 3.3 times at 26 weeks.The results of electron microscopy showed that the LDLR-/-rats had axonal injury at 15 weeks and aggravated gradually over time.At 26 weeks,Western blot analysis of the LDLR-/-rats showed that the MBP expression level of the corpus callosum area decreased significantly.Fast blue staining showed loosening of nerve fibers,diffuse vacuole formation,and myelinated nerve fiber loss in the corpus callosum area.In addition,it was also found that the number of oligodendrocytes in LDLR-/-rats was significantly reduced,and large numbers of astrocytes and microglia were activated.Conclusions LDLR-/-rats will have spontaneous hypercholesterolemia.Axonal injury,demyelination,decreased oligodendrocytes,as well as the abnormal activation of astrocytes and microglia are present in the early adult brain white matter area.

Objective To investigate association of the DTNBP1 gene polymorphisms with paranoid schizophrenia in Chinese Han populations by a two-stage study.Methods In the discovery stage, 11 SNPs in DTNBP1 were tested in 532 patients with paranoid schizophrenia and 488 controls by Sanger sequencing.In the validation sample (1 111 cases and 1 435 controls), Taqman genotyping method was used to genotype SNP rs4715986.Results In the discovery stage, SNP rs4715986 showed disease association (χ2=11.02, P<0.01) with paranoid schizophrenia for analysis of 532 patients and 488 controls;such an association survived a correction with 10 000 permutations (corrected P<0.05).In the validation sample (1 111 cases and 1 435 controls), we confirmed the genotypic association (χ2=9.292, P=0.01) of rs4715986 with paranoid schizophrenia.Conclusions The present results suggest that the DTNBP1 gene may be mainly involved in the development of paranoid schizophrenia in the Chinese Han population.

Objective To investigate epidermal growth factor receptor(EGFR)gene T790M mutation in plasmatic ctDNA samples from 171 patients with non-small cell lung cancer and analyze the relationship between EGFR T790M mutation and the clinical factors. Methods The EGFR T790M mutation was detected in 171 cases by super amplification refractory mutation system(Super ARMS)in this paper. Rusults The EGFR gene T790M mutation was identified in 7.60%(13/171)plasmatic ctDNA samples which mostly came from patients withⅢb~Ⅳstages of lung cancer. The EGFR T790M mutation rate was identified in 2.05%(3/146)plasmatic samples of pa-tients who did not received treatment of EGFR-TKIs,which was lower than 40.00%(10/25,P<0.05)plasmatic samples of patients who received treatment of first generational EGFR-TKIs. The EGFR T790M mutation rate was identified in 75.00%(3/4) and 60.00%(6/10) plasmatic samples of patients who have received TKI for 6 to 10 months and more than 10 months,which was higher than 9.10%(1/11,P < 0.05)plasmatic samples of patients who have received TKIs for less than 6 months. Conclusions This article demonstrated that EGFRT790M muta-tion was more common in lately NSCLC patients who have received TKIs treatmentover 6 months,meanwhile the EGFR T790M mutation dynamical detective technology will effectively guide the clinic treatment.