Hepatic COX1 loss leads to impaired autophagic flux and exacerbates nonalcoholic steatohepatitis

The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.

Six body indexes and typing characteristics of Xibe adults / 解剖学报

[Abstract] Objective To explore the body index and typing characteristics of Xibe nationality. Methods According to Anthropomatric Methods, height, chest circumference, sitting height, shoulder width, pelvic width and body mass morphological indexes were collected from 588 Xibe people in Yili area and 420 Xibe people over 18 years old in Shenyang area. After data collation, body index and typing were calculated and analyzed statistically. Results Except for Xibe male stature-shoulder breadth index and Caup’ s index in Yili area and female stature-shoulder breadth index in Shenyang area, there were differences among age groups in other indexes (P < 0. 05). Except for male stature-chest circumference index, stature-crista iliaca index, female stature-chest circumference index, stature-sitting height index, Manouvrier’s skelic index, there were differences among regions (P<0. 05). The adult body shape of Xibe nationality was mainly of wide chest, wide shoulder, long trunk, wide pelvis, medium leg and sub-long leg (male), sub-short leg and medium leg (female), and overweight. Conclusion There are regional and age differences in the body index and typing of Xibe adults. Compared with other ethnic minorities, Xibe nationality’s stature-chest circumference index, stature-shoulder breadth index, stature-crista iliaca index, Caup’s index are at a higher level. The proportion of legs and body of Xibe nationality is in the middle level, while the proportion of trunk is slightly shorter for men and slightly longer for women.

The reversal effect of albiflorin on multidrug resistance of human ovarian cancer and its mechanism / 中国药理学通报

Aim To study the reversal effect of albiflorin(AL)on multidrug resistance of human ovarian cancer and the potential mechanism. Methods The drug resistance reversal effect of AL on SKOV3/DDP cells was detected by CCK-8 kit,and the effect of AL on P-glycoprotein(P-gp)function was detected by flow cytometry. The effects of AL on MYC,WWP1 and ABCB1 in SKOV3/DDP cells were detected by RT-qPCR and Western blot. The MYC-knockdown SKOV3/DDP cell line was constructed by RNA interference technology,and its drug resistance,P-gp function and related gene and protein expression changes were investigated. Results AL had a drug resistance reversal effect on SKOV3/DDP cells and a concentration-dependent inhibitory effect on P-gp function. The inhibitory effects of AL 25,50 and 100 μmol·L-1 on ABCB1/P-gp,MYC and WWP1 were gradually enhanced. The inhibitory effect of MYCi975,a MYC inhibitor,on ABCB1/P-gp,MYC and WWP1 was stronger than or equivalent to that of AL 100 μmol·L-1 group. After knockdown of MYC in SKOV3/DDP cells,cell drug resistance,P-gp function,and related gene and protein expression were inhibited. Conclusions The drug resistance reversal effect of AL on SKOV3/DDP cells may be related to the inhibition of P-gp function and the expression of ABCB1/P-gp,MYC and WWP1,which provides an experiment base for the development of AL as a drug resistance reversal agent for the clinical treatment of ovarian cancer.

Clinical application of Chaihu Jia Longgu Muli Decoction based on modern pathophysiology mechanism / 中国中药杂志

Chaihu Jia Longgu Muli Decoction was firstly recorded in Treatise on Cold Damage(ZHANG Zhong-jing, Eastern Han dynasty). According to this medical classic, it is originally used in the treatment of the Shaoyang and Yangming syndrome. Based on the modern pathophysiological mechanism, this study interpreted the classic provisions of Chaihu Jia Longgu Muli Decoction. Original records of "chest fullness" "annoyance" "shock" "difficult urination" "delirium" "heavy body and failing to turn over" all have profound pathophysiological basis, involving disorders in cardiovascular, respiratory, nervous, and mental systems. This formula is widely used, which can be applied to treat epilepsy, cerebral arteriosclerosis, cerebral infarction, and other cerebrovascular diseases, hypertension, arrhythmia, and other cardiovascular diseases, insomnia, constipation, anxiety, depression, cardiac neurosis and other acute and chronic diseases as well as diseases in psychosomatic medicine. The clinical indications include Bupleuri Radix-targeted syndrome such as fullness and discomfort in chest and hypochondrium, bitter taste mouth, dry throat, and dizziness, the insomnia, anxiety, depression, susceptibility to fright, upset, dreamfulness and other psychiatric symptoms, red tongue, thick and yellow tongue coating, and wiry hard and powerful pulse. This formula was found to be used in combination with other formulas, such as Gualou Xiebai Decoction, Wendan Decoction, Zhizhu Pills, Juzhijiang Decoction, Suanzaoren Decoction, and Banxia Baizhu Tianma Decoction.

Establishment of An Animal Model of Acute B Lymphoblastic Leukemia with Minimal Residual Disease / 中国实验血液学杂志

OBJECTIVE@#To establish an animal model of acute B lymphoblastic leukemia (B-ALL) with minimal residual disease.@*METHODS@#The transplanted tumor was formed by subcutaneous injection of 2×107 Nalm-6 cells, and the body weight, activity status and tumor formation status of nude mice were observed. Peripheral blood, bone marrow, liver and spleen and other tissues of nude mice were taken for pathological examination to understand whether the success of subcutaneous modeling was accompanied by systemic metastasis.@*RESULTS@#There were 2×107 Nalm-6 cells injected subcutaneously in nude mice, (11.0±2.5) days later, the tumors of (3-4) × (3-4) mm were observed, the body weight of the nude mice was reduced and activity showed no limited. Infiltration of tumor cells in liver, spleen and bone marrow were observed in pathological sections.@*CONCLUSION@#The animal model of subcutaneous tumor of B-ALL was successfully established in nude mice.

Analysis of molecular and clinical characteristics of carbapenem-resistant hypervirulent Klebsiella pneumoniae in the intensive care unit / 中华预防医学杂志

To investigate the carbapenemases distribution of carbapenem-resistant Klebsiella pneumoniae (CRKP) in the intensive care unit, and the clinical characteristics between carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) and carbapenem-resistant non-hypervirulent Klebsiella pneumoniae (CR-non-hvKP) were compared. A total of 53 non-repetitive CRKP strains isolated from 49 patients in the intensive care unit of the Second Affiliated Hospital of Xi'an Jiaotong University from May 2020 to March 2021 were retrospectively studied. The carbapenemase inhibitor enhancement test was used for screening carbapenemase-producing strains, and the string test was carried out to screen the hypermucoviscosity phenotype. Using PCR to detect five main carbapenemase genes (blaKPC-2, blaNDM, blaIMP , blaVIM and blaOXA-48-like), common serotype (K1 and K2) and virulence gene (rmpA and iutA). Treated the strains with both rmpA and iutA genes as hypervirulent Klebsiella pneumonia (hvKP), and the whole genome sequencing of CR-hvKP was completed. At the same time, the clinical data of 49 patients were sorted out, and the differences in clinical characteristics of CR-hvKP and CR-non-hvKP infected patients were compared using the independent sample t test, Mann-Whitney U test, chi-square test or Fisher's exact probability test. CRKP isolated from the intensive care unit were extensively drug resistance and still had a good sensitivity to polymyxin B and tigecycline. Producing carbapenemases were the main resistance mechanism of CRKP (52/53, 98.1%). Of the 53 CRKP strains, except for 1strain that did not detect carbapenemase, at least one carbapenemase resistance gene was detected in the remaining 52 CRKP strains, of which 45 strains carried an enzyme, including 36 blaKPC-2 (36/53, 67.9%), 8 blaNDM (8/53, 15.1%), 1 blaIMP (1/53, 1.9%), and 7 strains carried with both blaKPC-2 and blaNDM (7/53, 13.2%). String test and virulence gene showed that 7 CR-hvKP strains (13.2%) were detected in 53 CRKP strains, and two of which were hypermucoviscosity phenotype. Sequencing results revealed that CR-hvKP were mainly ST11 type. Almost all patients with CR-hvKP infection were over 60 years old (7/7), with invasive treatment (7/7), pulmonary infection with hypermucoviscosity phenotype (2/7) and high mortality (5/7); and the percentage of neutrophils in patients with CR-hvKP infection (86.44±4.70) % was higher than those patients with CR-non-hvKP infection (78.90±19.15) %, the difference was statistically significant (t=-2.225, P=0.032). The CR-hvKP strains in the intensive care unit mainly produced KPC-2 enzyme, with K2 capsular serotype and ST11 type. It is necessary to strengthen the monitoring and control of the CR-hvKP strain to prevent the co-evolution of drug-resistant and hypervirulent strains.

Lodderomyces elongisporus causing catheter-related bloodstream infection and its biological characteristics / 中华检验医学杂志

In order to improve the laboratory identification ability of Lodderomyces elongisporus, we analyzed the main biological characteristics of Lodderomyces elongisporus isolated from peripheral venous blood and catheter blood of a brain stem infarction patient with a body temperature of 38.4 ℃, observed the colony color of the strain on CHROMagar Candida medium and the ascospores on Mcclary agar, identified the isolates with Vitek 2 compact, MALDI-TOF MS and sequence analysis, and tested the MICs with borth microdilution. The MICs of antifungal agents against Lodderomyces elongisporus are well below the normal values of these drugs. The central venous catheter was removed and antifungal drugs were used until two weeks after the last positive blood culture. During the medication perios, the blood culture was repeatedly negative, the patient had no fever and the infection index decreased to normal, which can be used for clinical reference.

Effect of Wenyang Huazhuo Tongluo formula on Sema3A/Nrpl signaling pathway in systemic sclerosis mouse model / 中国药理学通报

Aim To study the effeet of Wenyang Hua- Nrpl signaling pathway in systemic sclerosis ( SSc ) zhuo Tongluo formula ( WYHZTLF) on the Sema3A/ mouse model, and to explore its mechanism in the treatment of SSe.Methods The systemic sclerosis mouse model was constructed and divided into control group, model group, WYHZTLF low (21 g • kg 1 ) , medium (42 g • kg 1 ) , high (84 g • kg 1 ) dose group and the Sema3A inhibitor epigallocatechol gallate (EGCG) group.All groups were given intragastric administration for four weeks, and the control and model groups were treated with saline.Histopathology and dermal thickness were detected by HE, VEGFA pro-tein expression levels were detected by immunohisto- chemistry; the protein expression levels of Sema3A, Nrpl and VEGFA were determined by Western blot; Sema3A expression levels in mouse serum were detec-terl by ELISA.Results Comparer] with model group, WYHZTLF significantly alleviated the skin lesions in systemic sclerosis mouse model, significantly inhibited the dermal thickness, inhibited the protein expression levels of VEGFA, Sema3A and Nrpl , and reduced the expression levels of serum Sema3A.Conclusion WYHZTLF can improve the vascular injury of SSc, and its mechanism may be related to the inhibition of VEGFA and Sema3A/Nrpl signaling pathway.

Fertility and reproduction in rats with metabolic syndrome / 上海预防医学

Objective To study the effect of metabolic syndrome on the fertility and reproduction in model animals. Methods The model of"high fat diet for spontaneously hypertensive rats(SHR)"was adopted to construct the model of metabolic syndrome in rats. The metabolic syndrome model rats were used to mate with male and female 1 : 1 cage, and the mating cycle was 2 weeks. Results After the SHR rats were fed a high-fat diet for 10 weeks, 16 males and 15 females met the screening criteria for metabolic syndrome, with the modeling rates of 40% and 37.5%, respectively. In addition to the abnormal metabolism-related indicators(such as blood glucose, blood lipid and blood pressure), the male rats with metabolic syndrome mainly had decreased sperm motility(P < 0.05), increased sperm malformation rate(P < 0.01), and decreased mating rate(P < 0.05). In addition to abnormal metabolism-related indicators, the conception rate and the live fetal rate of the female rats with metabolic syndrome were slightly lower than that of the control group; however, there was no statistical difference. The mean birth weight of the litter was significantly lower than that of the control group(P < 0.05). Conclusion According to the whole process from mating to natural production, metabolic syndrome is determined to have a significant effect on the fertility and reproductive ability of rats.

Treatment strategy and thought on classical herbal formulae for coronavirus disease 2019 / 中国中药杂志

Coronavirus disease 2019(COVID-19) refers to the pneumonia caused by novel coronavirus(2019-nCoV) infection in 2019. It is highly infectious, with quick spreading and a wide range of impact. It has been broken out in many countries around the world and has become a public health emergency of international concern. Chinese medicine has a long history in treating plague, and viral disease is the clinical advantage in Chinese medicine. Under the premise that there is currently no specific drug treatment, Chinese medicine has achieved certain effects in the treatment of COVID-19, which has attracted much attention and has been upgraded to a national strategy. Regarding the treatment of COVID-19 with Chinese medicine, it is believed that in terms of the name of Chinese medicine, the modern connotation of "uniform of typhoid and febrile disease" should be re-recognized, and it is advisable to use drugs based on specific clinical prescriptions and indications. In terms of pathogenesis, the COVID-19 has the pathogenesis rules including from the mild to severe conditions, from the surface to the inside, from the excess syndrome to the deficiency syndrome. We should pay attention to the Taiyang syndrome damaged by wet disease in initial stage, Shaoyang syndrome complicated with Yangming syndrome in the middle stage, phlegm-heat obstructing lung in critical period, lung and spleen deficiency in the recovery stage. In terms of clinical treatment strategies, Dayuan Yin is recommended to induce sweat and disperse the stasis in early stage. Xiaochaihu Decoction and Maxing Shigan Decoction is used to relieve both exterior and interior symptoms in middle stage. In critical stage, Tingli Dazao Xiefei Decoction, Weijing Decoction, Xuanbai Chengqi Decoction, Xiaoxianxiong Decoction, and Sanzi Yangqin Decoction are considered to reduce phlegm and clear heat. We should pay attention to nourishing Qi and strengthening the spleen by Zhuye Shigao Decoction, Sha-shen Maidong Decoction, and Liujunzi Decoction in the later recovery period. It shall be noted that, no matter in the initial mild stage, the middle and critical stages, or in the later recovery stage, Chinese medicine plays an important role, including preventing mild to severe disease, shortening the fever time, improving cough symptoms, increasing blood oxygen saturation and reducing mortality. Many studies have shown that the classical herbal formulae can alleviate the cytokine storm, regulate the immune imbalance, and produce the potential effect of synergistic treatment for COVID-19 through multiple components, multiple targets, and multiple pathways.

Clinical study on endoscopic surgery for soft tissue necrosis of cranial base after radiotherapy for nasopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the diagnosis and surgical treatment of patients with soft tissue necrosis of cranial base after radiotherapy for nasopharyngeal carcinoma (NPC). Methods: The clinical data of 7 NPC patients with soft tissue necrosis but not bone necrosis after radiotherapy were retrospectively analyzed.They were treated in Xiangya Hospital from 2015 to 2019. The clinical manifestations, diagnosis, treatment and prognosis were analyzed. The major clinical symptoms of the 7 patients were headache in 7 cases, hearing loss in 7 cases, long-term nasal malodor in 5 cases and epistaxis in 2 cases. All patients underwent high-resolution CT, MR and magnetic resonance angiography (MRA) before operation. All cases were treated with extended transnasal endoscopic approach under general anesthesia for resection of necrotic tissue. Five cases had their affected cartilaginous segments of the eustachian tubes partially or completely resected, 7 cases were treated with myringotomy and tube insertion, and 1 case was treated with pansinusectomy. Anti-inflammatory treatment were carried out during the perioperative period. The recovery of patients was observed and recorded through regular follow-up (from 6 months to 3 years) after the operation. Results: Nasopharynx soft tissue lesions can be seen in seven patients with bone cortex integrity by CT, and small bubble shadow can be seen at junction area between skull base soft tissue lesions and skull base bone surface.MR and MRA examination showed extensive inflammatory changes of nasopharynx. Parapharyngeal irregular necrotic cavity was found in 6 cases without central enhancement, demonstrating edema of surrounding soft tissue. The necrotic tissue of all 7 patients was surgically removed. Postoperative pathological examinations confirmed that all of them were necrotic soft and cartilaginous tissue, without tumor recurrence. The symptoms of all patients were significantly alleviated after operation. Headache was cured in 5 cases and relieved in 2 cases. Nasal malodor was cured in 4 cases and alleviated in 1 case. During the follow-up period, 5 patients survived, and 2 patients who had their eustachian tube reserved died. One of them died of nasopharyngeal hemorrhage caused by recurrent nasopharyngeal necrosis 3 months after the operation. Another case died of severe intracranial infection 6 months after operation. Conclusions: The diagnosis of skull base soft tissue necrosis after radiotherapy for nasopharyngeal carcinoma needs comprehensive analysis of radiotherapy history, clinical manifestations and imaging examination. High resolution CT, MR and MRA of skull base are very important for diagnosis. Early active removal of large-scale necrotic lesions under endoscope and partial or total resection of eustachian tube cartilage according to the involvement of eustachian tube cartilage is effective means of controling skull base soft tissue necrosis after radiotherapy. The effective means of necrosis can improve the quality of life of patients.

Analysis of clinical features and genetic variants in an infant with Bloom syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical features and genetic variants in a 13-month-old child with Bloom syndrome.@*METHODS@#Clinical data of the child was collected. Genetic variants were detected by high-throughput sequencing and Sanger sequencing.@*RESULTS@#The child was born at full term but was small for gestational age. His clinical features included loss of appetite, severe growth retardation, microcephaly, and small mandible. Genetic testing found that he had carried compound heterozygous c.1068+3A>C and c.1069-1G>C variants of the BLM gene, both of which were unreported previously.@*CONCLUSION@#Bloom syndrome is mainly characterized by severe growth retardation in infancy. The novel variants have expanded the variant spectrum of the BLM gene.

Effect of 1, 25-dihydroxy vitamin D3 on food allergy in mice / 中华实用儿科临床杂志

Objective@#To investigate the effects of 1, 25-dihydroxy vitamin D3[1, 25(OH)2D3] on food allergy(FA) in mice and its mechanism.@*Methods@#A total of 40 BALB/c mice were randomly divided into 5 groups, 8 in each group, including control group (group C) and FA model group (FA group), according to the dose of 1, 25(OH)2D3 intervention, the mice of the FA group were divided into FA0 group (0), FAl group [10 μg/(kg·d)], FAm group [50 μg/(kg·d)] and FAh group[100 μg/(kg·d)]. Egg albumin was used to establish a food allergy model, with different doses of 1, 25(OH)2D3 for gastric intervention, and the control group was replaced by 9 g/L saline.The serum levels of ovalbumin-immunoglobulin E(OVA-IgE), interleukin(IL)-9 and IL-17 of mice were measured by using enzyme linked immunosorbent assay after the last excitation, and HE staining and histopathological examination were carried out in the small intestine of mice.@*Results@#Compared with group C, FA0 group and FAh group small intestinal mucosa in mice had different degrees of damage, partial peeling off, structure disorder, villi epithelial cell focal falls peeling off, necrosis, lamina propria edema, congestion, a large number of inflammatory cells infiltration, low but the FAl group and FAm group had light mucosa damage, intestinal epithelial basically intact, with integrity, no congestion, edema, and inflammatory cells infiltration to a lesser degree.The mean concentrations of serum IgE, IL-9 and IL-17 in different groups were statistically significant (F=40.770, 9.530, 5.624, all P<0.05). Compared with the FA0 group [(41.87±3.19) ng/L], the OVA-IgE of the FAl group [(22.71±4.77) ng/L] and the FAm group [(16.34±2.81) ng/L] were significantly reduced (t=5.533, 11.835, all P<0.01), but there was no significant difference between the FAh group [(36.29±6.52) ng/L] (t=1.673, P>0.05). Compared with the FA0 group [(161.77±50.44) ng/L], the IL-9 levels of the FAl group [(94.29±18.79) ng/L] and the FAm group[(84.45±30.88) ng/L] were significantly lower (t=3.267, 3.366, all P<0.01), while that of the FAh group [(36.29±6.52) ng/L] was not significantly lower (t=0.777, P>0.05). Compared with FA0 group [(81.55±29.37) ng/L], IL-17 levels of FAh group [(133.58±47.05) ng/L] was significantly increased (t=2.653, P<0.05), while IL-17 level of FAl group [(79.41±25.15) ng/L] and FAm group [(58.81±26.00) ng/L] were lower than that of FA0 group [(81.55±29.37) ng/L], but the difference was not statistically significant (t=0.154, 1.640, all P>0.05).@*Conclusions@#Low, medium dose of 1, 25(OH)2D3 supplements can inhibit mice food allergies, but high doses of 1, 25(OH)2D3 improve performance in mice food allergies, and 1, 25(OH)2D3′s influence on the secretion of IL-9 is one that influences mechanism of food allergy.

Effect of 1,25-dihydroxy vitamin D3 on food allergy in mice / 中华实用儿科临床杂志

Objective To investigate the effects of 1,25-dihydroxy vitamin D3 [1,25 (OH)2D3] on food allergy(FA) in mice and its mechanism.Methods A total of 40 BALB/c mice were randomly divided into 5 groups,8 in each group,including control group (group C) and FA model group (FA group),according to the dose of 1,25 (OH)2 D3 intervention,the mice of the FA group were divided into FA0 group (0),FA1 group [10 μg/(kg · d)],FAm group [50 μg/(kg · d)] and FAh group[100 μg/(kg · d)].Egg albumin was used to establish a food allergy model,with different doses of 1,25 (OH)2D3 for gastric intervention,and the control group was replaced by 9 g/L saline.The serum levels of ovalbumin-immunoglobulin E(OVA-IgE),interleukin (IL)-9 and IL-17 of mice were measured by using enzyme linked immunosorbent assay after the last excitation,and HE staining and histopathological examination were carried out in the small intestine of mice.Results Compared with group C,FAo group and FAh group small intestinal mucosa in mice had different degrees of damage,partial peeling off,structure disorder,villi epithelial cell focal falls peeling off,necrosis,lamina propria edema,congestion,a large number of inflammatory cells infiltration,low but the FA1 group and FAm group had light mucosa damage,intestinal epithelial basically intact,with integrity,no congestion,edema,and inflammatory cells infiltration to a lesser degree.The mean concentrations of serum IgE,IL-9 and IL-17 in different groups were statistically significant (F =40.770,9.530,5.624,all P ＜ 0.05).Compared with the FA0 group [(41.87 ±3.19) ng/L],the OVA-IgE of the FA1 group [(22.71 ±4.77) ng/L] and the FAm group [(16.34 ±2.81) ng/L] were significantly reduced (t =5.533,1 1.835,all P ＜ 0.01),but there was no significant difference between the FAh group [(36.29 ± 6.52) ng/L] (t =1.673,P ＞ 0.05).Compared with the FA0 group [(161.77 ±50.44) ng/L],the IL-9 levels of the FA1 group [(94.29 ± 18.79) ng/L] and the FAm group [(84.45 ± 30.88) ng/L] were significantly lower (t =3.267,3.366,all P ＜ 0.01),while that of the FAh group [(36.29 ±6.52) ng/L] was not significantly lower (t =0.777,P ＞0.05).Compared with FA0 group [(81.55 ±29.37) ng/L],IL-17 levels of FAh group [(133.58 ± 47.05) ng/L] was significantly increased (t =2.653,P ＜0.05),while IL-17 level of FA1 group [(79.41 ± 25.15) ng/L] and FAm group [(58.81 ± 26.00) ng/L] were lower than that of FAo group [(81.55 ±29.37) ng/L],but the difference was not statistically significant (t =0.154,1.640,all P ＞ 0.05).Conclusions Low,medium dose of 1,25 (OH) 2 D3 supplements can inhibit mice food allergies,but high doses of 1,25 (OH)2 D3 improve performance in mice food allergies,and 1,25 (OH)2 D3's influence on the secretion of IL-9 is one that influences mechanism of food allergy.

Role of hypomethylation of suppressor of cytokine signaling in T helper 17 cell/regulatory T cell imbalance in children with Henoch-Schönlein purpura / 中国当代儿科杂志

OBJECTIVE@#To investigate the association between suppressor of cytokine signaling (SOCS) hypomethylation and T helper 17 (Th17) cell/regulatory T (Treg) cell imbalance in children with Henoch-Schönlein purpura (HSP) and the immune pathogenesis of HSP.@*METHODS@#A total of 32 children in the acute stage of HSP who were hospitalized from May 2014 to January 2015 were enrolled as subjects, and 28 children who underwent physical examination were enrolled as normal control group. ELISA was used to measure the plasma level of interleukin-6 (IL-6). Flow cytometry was used to measure the percentages of CD4 IL-17A T cells (Th17 cells) and CD4CD25 Treg cells (Treg cells) in peripheral blood and mean fluorescence intensity (MFI) for phosphorylated-STAT3 (pSTAT3) protein in CD4 T cells. Quantitative real-time PCR was used to measure the mRNA expression of suppressor of cytokine signaling-1 (SOCS1) and suppressor of cytokine signaling-3 (SOCS3) in CD4 T cells. High-resolution melting (HRM) was used to evaluate the methylation level of the CpG islands in SOCS1 exon 2 and the CpG islands of the potential bind sites for STAT3 in the 5'-untranslated region (5'-UTR) of SOCS3 in peripheral blood mononucleated cells.@*RESULTS@#Compared with the normal control group, the HSP group had significant increases in plasma IL-6 concentration and MFI for pSTAT3 in CD4 T cells, as well as a significant increase in the percentage of Th17 cells and a significant reduction in the percentage of Treg cells (P<0.05). The HSP group had significantly higher mRNA expression of SOCS1 and SOCS3 in peripheral blood mononucleated cells than the normal control group (P<0.05). In the HSP group, the mRNA expression of SOCS1 and SOCS3 was negatively correlated with Th17/Treg ratio (P<0.05). The HSP group had hypomethylation of the CpG islands in SOCS1 exon 2 and the potential binding site for STAT3 in SOCS3 5'-UTR, while the normal control group had complete demethylation.@*CONCLUSIONS@#Low relative expression of SOCS1 and SOCS3 caused by hypomethylation may be a factor for Th17/Treg imbalance in children with HSP.

Application of cream formula in treatment of severe heart failure / 中国中药杂志

Cream formula has been mostly used to treat deficiency syndrome. Currently,it has been used to recuperate the body,promote health against aging,and prevent and treat chronic disease. In modern medicine,there are only treatment concepts and methods of diseases,but lack of concepts of " deficiency syndrome" and " restoring deficiency". The concepts of " deficiency syndrome" and " restoring deficiency" could effectively supplement and improve the diagnosis and treatment scheme of some modern diseases. Refractory heart failure,dilated cardiomyopathy,ischemic cardiomyopathy,and valvular heart disease belong to the traditional category of " consumptive disease". The cream formula with the efficacy of restoring deficiency can not only alleviate symptoms and improve the quality of life,but also improve the structure and function of the heart,reduce the dosage of diuretics and the number of hospitalizations,and achieve the purpose of secondary prevention in the treatment of severe heart failure,dilated cardiomyopathy,ischemic cardiomyopathy and valvular heart disease. The cream formula for treating chronic heart failure include Shenqi Pills,Zhenwu Decoction,Yougui Pills,Wuling Powder,Linggui Zhugan Decoction,Danggui Shaoyao Powder,Lizhong Decoction,Buzhong Yiqi Decoction,Guipi Decoction,Yupingfeng Powder,Guizhi Decoction. Long-term administration of cream formula could not only resist aging,but also play an irreplaceable role in the secondary prevention of acute and critical diseases.

Vomiting, weakness and glyceroluria after eating dessert / 中华实用儿科临床杂志

During 2 years,a 6-year-old girl was hospitalized for 2 times with recurrent onset of episodes of vomiting,weakness and fever after eating dessert at the Department of Neurology & Endocrine Pediatrics,the Affiliated Hospital of Qingdao University.The arterial blood gas analysis revealed severe hypoglycemia,lacticacidemia and metabolic acidosis,the urine ketone body was positive.After intravenous infusion of glucose,bicarbonate and antibiotics,there was a dramatic clinical improvement in a short time.Physical examination showed tachypnea and mild hepatomegaly,and she had normal physical and mental development.The laboratory findings revealed transient hyperuricacidemia.Urine organic acids analysis repeatedly showed an elevation of lactic acid,ketone and glycerol.Glyceroluria was a very distinctive trait.The literatures in PubMed was searched with glyceroluria as keyword.Three related diseases were identified:FBPase deficiency,glycerol kinase (GK) deficiency and complex GK deficiency.Further reading of related literatures to understand the characteristics of diseases and laboratory tests,the clinical diagnosis of GK deficiency and complex GK deficiency was excluded.The mutation analysis of FBPase gene (FBP1) was performed by Sanger sequencing and a novel compound heterozygous mutations of c.355G ＞A and c.960delG was discovered.Full analysis of disease-related traits and targeted gene testing is one of the effective methods for accurate diagnosis and treatment of inherited metabolic disorders.

Novel mutations of ITGB2 induced leukocyte adhesion defect type 1 / 中华儿科杂志

Objective@#To investigate the pathogenic mechanism of two novel ITGB2 mutations in leukocyte adhesion defect type 1 (LAD1).@*Methods@#The clinical history and blood sample of an 11 years old patient admitted to Affiliated Hospital of Qingdao University in August 2014 were collected. Expression of CD18 (encoded by ITGB2) was analyzed by flow cytometry. Novel ITGB2 mutations were identified by next-generation sequencing technology and confirmed by Sanger sequencing. The functional effect of ITGB2 mutations was detected by PolyPhen2. Expression vectors of both wild type and mutant ITGB2 were constructed and transfected into mammalian cells for analysis of protein stability and subcellular location.@*Results@#The symptoms of the patient (recurrent infections, lowered alveolar ridge and hypodontia) supported the diagnosis of LAD1. Expression of CD18 on the leukocytes was significantly decreased (0.2%) compared with the control samples from the parents (paternal: 99.0%; maternal: 99.1%). The patient was identified to be compound heterozygous for ITBG2 c.954del G (novel mutation) and c.1802C>A (paternal originated). ITGB2 c.954 del G was confirmed to be a harmful frameshift mutation; ITGB2 c.1802C>A was also predicted to be harmful. In terms of protein stability. There was no significant difference between mutant D18 and wild type. However, subcellular location analysis showed the mutant D18 could not locate on cell membrane.@*Conclusion@#The compound heterozygous of ITGB2 mutations (c.954del G and c.1802C>A) decreases the expression and impairs the location of CD18 on leukocytes, which leads to LAD1.

Thought and method of classic formulae in treatment of chronic cough / 中国中药杂志

Chronic cough is a common clinical disease with complex etiology, which is easily misdiagnosed and mistreated. Chronic cough guideline has been developed based on the modern anatomical etiology classification, and it may improve the level of diagnosis and treatment. Common causes of chronic cough are as follows: cough variant asthma, upper airway cough syndrome, eosinophilic bronchitis, gastroesophageal reflux-related cough, post-infectious cough, etc. There is a long history and rich experience in treatment of cough in traditional Chinese medicine which is characterized by syndrome differentiation. The four elements of pathogenesis for chronic cough include wind, phlegm, fire, and deficiency. Classic formula is widely used in the treatment of chronic cough, and the focus is on prescriptions corresponding to syndromes. This article attempts to explore the thought and method of classic formulae in treatment of chronic cough based on three perspectives: differentiation of etiology, pathogenesis and formula-syndrome. Three medical cases are selected at last in order to prove its correction.

High Spicy Food Intake and Risk of Cancer: A Meta-analysis of Case-control Studies / 中华医学杂志(英文版)

<p><b>Background:</b>Studies on the association between spicy food intake and cancer risk have reported inconsistent results. We quantitatively assessed this association by conducting a meta-analysis based on evidence from case-control studies.</p><p><b>Methods:</b>PubMed, EMBASE, and the Cochrane Library were searched for eligible publications. Combined odds ratios (OR s) with their 95% confidence interval (CI) were calculated using a random- or fixed-effects model. The methodological quality of the included articles was assessed using the Newcastle-Ottawa scale (NOS). All data were analyzed using STATA 11.0 software (version 11.0; StataCorp., College Station, TX, USA). Subgroup analyses were also performed with stratification by region, sex, number of cases, cancer subtype, source of the control group, and NOS score.</p><p><b>Results:</b>A total 39 studies from 28 articles fulfilled the inclusion criteria for the meta-analysis (7884 patients with cancer and 10,142 controls). Comparison of the highest versus lowest exposure category in each study revealed a significant OR of 1.76 (95% CI = 1.35-2.29) in spite of significant heterogeneity (P < 0.001). In the subgroup analyses, this positive correlation was still found for gastric cancer, different regions, different numbers of cases, different sources of the control group, and high-quality articles (NOS score of ≥ 7). However, no statistically significant association was observed for women, esophageal cancer, gallbladder cancer, or low-quality articles (NOS score of <7). No evidence of publication bias was found.</p><p><b>Conclusions:</b>Evidence from case-control studies suggested that a higher level of spicy food intake may be associated with an increased incidence of cancer despite significant heterogeneity. More studies are warranted to clarify our understanding of the association between high spicy food intake and the risk of cancer.</p>