[Abstract] Objective To explore the inhibitory effect of sodium ferulate (SF) on the inflammatory response in migraine rats by regulating the c-Jun N-terminal kinase (JNK) / p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. Methods The migraine rat model was prepared by intraperitoneal injection of nitroglycerin. After successful modeling, the rats were randomly grouped into model group, SF low dose (SF-L) group (50 mg/ kg), SF high dose (SF-H) group (100 mg/ kg), SF+JNK inhibitor (SF + SP600125) group (SF 100 mg/ kg +SP600125 10 mg/ kg), and SF+JNK activator [SF + anisomycin(AN)] group (SF 100 mg/ kg +AN 5 mg/ kg), 12 in each group, another 12 SD rats without treatment were taken as blank group. The behavioral changes of the rats in each group were observed 24 hours after the administration, the levels of 5-hydroxytryptamine (5-HT), nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum were detected by ELISA, the neuronal apoptosis in brain tissue was observed by TUNEL staining, immunohistochemistry was used to evaluate the expressions of TNF-α, IL-6 and calcitonin gene-related peptide (CGRP) in brain tissue, Western blotting was used to detect the expressions of JNK/ p38 MAPK pathway-related proteins in brain tissue. Results Compared with the blank group, the number of times of scratching the head and climbing the cage of the rats in the model group increased significantly, and the apoptosis rate of neurons increased significantly; the content of 5-HT in serum decreased significantly, and the levels of NO, TNF-α and IL-6 increased significantly; the expressions of TNF-α, IL-6 and CGRP, and the ratios of phosphorylated JNK (p-JNK) / JNK and phosphorylated p38 MAPK(p-p38 MAPK) / p38 MAPK in brain tissue obviously increased (all P<0. 05). Compared with the model group, the number of times of scratching the head and the times of climbing the cage of the rats in the SF-L group and the SF-H group reduced significantly, and the neuron apoptosis rate reduced significantly; the content of 5-HT in serum increased significantly, and the levels of NO, TNF-α and IL-6 decreased significantly; the expressions of TNF-α, IL-6 and CGRP, and the ratios of p-JNK/ JNK and p-p38 MAPK/ p38 MAPK in brain tissue obviously decreased (all P<0. 05). Compared with SF-H group, the protective effect of SF on migraine rats in SF+SP600125 group enhanced significantly; the protective effect of SF on migraine rats in the SF+AN group reversed significantly. Conclusion SF may inhibit the expression of JNK/ p38 MAPK signaling pathway, effectively inhibit neurogenic inflammatory response in migraine rats, reduce neuronal apoptosis, and achieve a protective effect on migraine rats.

Lung and intestine combination therapy(LICT) is effective in the treatment of acute lung injury(ALI). In this study, the combination of Mahuang Decoction and Dachengqi Decoction(hereinafter referred to as the combination), a manifestation of LICT, was employed to explore the effect of nuclear factor kappaB(NF-κB)/nucleotide binding oligomerization domain-like receptors-3(NLRP3) pathway and alveolar macrophage activation on the lung inflammation in rats with ALI, for the purpose of elucidating the mechanism of LICT in treating ALI. After the modeling of ALI with limpolysaccharide(LPS, ip), rats were respectively given(ig) the combination at 10, 7.5, and 5 g·kg~(-1)(high-dose, medium-dose, and low-dose LICT groups, separately), once every 8 h for 3 times. Haematoxylin-eosin(HE) staining was used to observe the histopathological changes of lung tissue, followed by the scoring of inflammation. Immunohistochemistry was applied to detect alveolar macrophage activation, enzyme-linked immunosorbent assay(ELISA) was applied to detect the serum content of tumor necrosis factor-α(TNF-α) and interleukin-18(IL-18), Western blot was applied to detect the protein expression of phosphorylated-nuclear factor kappaB p65(p-NF-κB p65), nuclear factor kappaB p65(NF-κB p65), phosphorylated-inhibitor kappaB alpha(p-IκBα), inhibitor kappaB alpha(IκBα), and NLRP3 in lung tissue, and quantitative reverse transcription-PCR(qRT-PCR) was applied to detect the mRNA expression of TNF-α, IL-18, NLRP3, and NF-κB p65 in lung tissue. The results showed that LICT groups demonstrated lung injury relief, decrease in inflammation score, alleviation of alveolar macrophage activation, significant decline in serum content of inflammatory factors TNF-α and IL-18, and decrease of the protein expression of p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3, and mRNA expression of TNF-α, IL-18, NLRP3, and NF-κB p65 in lung tissue. In summary, LICT has definite therapeutic effect on ALI. The mechanism is that it inhibits alveolar macrophage activation by suppressing NF-κB/NLRP3 signaling pathway, thereby reducing the activation and release of inflammatory factors and finally inhibiting inflammation.
Acute Lung Injury/genetics* ; Animals ; Drugs, Chinese Herbal ; Intestines ; Lipopolysaccharides ; Lung/metabolism* ; Macrophage Activation ; NF-kappa B/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Rats ; Signal Transduction

Objective: To analyze the current adherence to imatinib in patients with gastrointestinal stromal tumors (GIST) in China and its influencing factors. Methods: A cross-sectional survey was conducted. Study period: from October 1, 2020 to November 31, 2020. Study subjects: GIST patients taking imatinib who were diagnosed and treated in public tertiary level A general hospitals or oncology hospitals; those who had not been pathologically diagnosed, those who never received imatinib, or those who had taken imatinib in the past but stopped afterwards were excluded. The Questionnaire Star online surgery platform was used to design a questionnaire about the adherence to adjuvant imatinib therapy of Chinese GIST patients. The link of questionnaire was sent through WeChat. The questionnaire contained basic information of patients, medication status and Morisky Medication Adherence Scale. Results: A total of 2162 questionnaires from 31 provinces, autonomous regions, and municipalities were collected, of which 2005 were valid questionnaires, with an effective rate of 92.7%. The survey subjects included 1104 males and 901 females, with a median age of 56 (22-91) years old. Working status: 609 cases (30.4%) in the work unit, 729 cases (36.4%) of retirement, 667 cases of flexible employment or unemployment (33.3%). Education level: 477 cases (23.8%) with bachelor degree or above, 658 cases (32.8%) of high school, 782 cases (39.0%) of elementary or junior high school, 88 cases (4.4%) without education. Marital status: 1789 cases (89.2%) were married, 179 cases (8.9%) divorced or widowed, 37 cases (1.8%) unmarried. Two hundred and ninety-four patients (14.7%) had metastasis when they were first diagnosed, including 203 liver metastases, 52 peritoneal metastases, and 39 other metastases. One thousand eight hundred and sixty-nine patients underwent surgical treatment, of whom 1642 (81.9%) achieved complete resection. The median time of taking imatinib was 25 (1-200) months. Common adverse reactions of imatinib included 1701 cases (84.8%) of periorbital edema, 1031 cases (51.4%) of leukopenia, 948 cases (47.3%) of fatigue, 781 cases (39.0%) of nausea and vomiting, 709 cases (35.4%) of rash, and 670 cases (33.4%) of lower extremity edema. The score of the Morisky Medication Adherence Scale showed that 392 cases (19.6%) had poor adherence, 1023 cases (51.0%) had moderate adherence, and 590 cases (29.4%) had good adherence. Univariate analysis showed that gender, age, work status, economic income, residence, education level, marriage, the duration of taking medication and adverse reactions were associated with adherence to adjuvant imatinib therapy (all P<0.05). Multivariate analysis showed that female (OR=1.264, P=0.009), non-retirement (OR=1.454, P=0.001), monthly income ≤4000 yuan (OR=1.280, P=0.036), township residents (OR=1.332, P=0.005), unmarried or divorced or widowed (OR=1.362, P=0.026), the duration of imatinib medication >36 months (OR=1.478, P<0.001) and adverse reactions (OR=1.719, P=0.048) were independent risk factors for poor adherence to adjuvant imatinib. Among patients undergoing complete resection, 324 (19.7%) had poor adherence, 836 (50.9%) had moderate adherence, and 482 (29.4%) had good adherence. Meanwhile, 55 patients with good adherence (11.4%) developed recurrence after surgery, 121 patients with moderate adherence (14.5%) developed recurrence, 61 patients with poor adherence (18.8%) developed recurrence, and the difference was statistically significant (P=0.017). Conclusions: The adherence to adjuvant therapy with imatinib in Chinese GIST patients is relatively poor. Females, non-retirement, monthly income ≤4000 yuan, township residents, unmarried or divorced or widowed, the duration of imatinib medication >36 months, and adverse reactions are independently associated with poor adherence of GIST patients. Those with poor adherence have a higher risk of recurrence after surgery. Positive interventions based on the above risk factors are advocated to improve the prognosis of patients with GIST.
Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use* ; Chemotherapy, Adjuvant ; Cross-Sectional Studies ; Female ; Gastrointestinal Stromal Tumors/drug therapy* ; Humans ; Imatinib Mesylate/therapeutic use* ; Male ; Middle Aged ; Neoplasm Recurrence, Local/drug therapy*

Atomic force microscope ( AFM) and fluorescence microscope ( FM) have been emerging as two most commonly used tools for single-molecule study in living cells. Combining the advantages of two microscopes, the development of the integrated AFM-FM technique with high spatiotemporal resolution and multi-function has attracted increasing interest. In this review, the principles of AFM single-molecular force spectroscopy and single-molecule fluorescence imaging were briefly discussed, and the recent advances in the integrated AFM-FM instrumentation were summarized. Subsequently based on our own research in the investigation of ligand-receptors interactions with the integrated AFM-FM technique, its applications in live-cell single-molecule imaging and characterization were introduced.

Dyslipidemia is a risk factor for cardiovascular diseases (CVDs) in patients with diabetes, and non-high-density lipoprotein cholesterol (non-HDL-C) is a better predictor of CVDs than low-density lipoprotein cholesterol (LDL-C) in patients with diabetes. Therefore, we aimed to investigate the distribution of non-HDL-C and the prevalence of high non-HDL-C level in Chinese patients with diabetes mellitus and identify the associated risk factors. Non-HDL-C concentration positively correlated with total cholesterol, triglycerides, and LDL-C concentrations. Although both non-HDL-C and LDL-C concentration both related positively with TC concentration, the magnitude of correlation was relatively higher for non-HDL-C. The prevalence of high non-HDL-C (⋝4.14 mmol/L) was higher in two age groups (55-64 years: 46.7%; 65-79 years: 47.3%) than other age groups (18-24 years: 4.2%; 25-34 years: 43.6%; 35-44 years: 38.1%; 45-54 years: 41.0%). It was also higher among overweight (45.1%), generally obese (50.9%), or abdominally obese (47.3%) subjects, compared with normal weight subjects (34.5%). The risk of high non-HDL-C increased with advancing age. Both general obesity [odds ratio (OR)=1.488, 95% confidence interval (CI): 1.003-2.209] and abdominal obesity (OR=1.561, 95% CI: 1.101-2.214) were significantly associated with high non-HDL-C levels.
Adolescent ; Adult ; China ; epidemiology ; Cross-Sectional Studies ; Diabetes Mellitus ; epidemiology ; etiology ; Female ; Humans ; Hypercholesterolemia ; epidemiology ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Young Adult

OBJECTIVETo investigate the influence of seasons, blood types and semen parameters on the cryosurvival rate of frozen-thawed spermatozoa from sperm donors.

METHODSWe retrospectively analyzed the influence of seasons, blood types, abstinence period, semen volume, sperm morphology, and pre-freeze sperm motility and concentration on the cryosurvival rate of frozen-thawed sperm in 4 088 semen samples from Shaanxi Human Sperm Bank.

RESULTSThe cryosurvival rate of the post-thaw sperm was correlated negatively with the progressive motility of the pre-freeze sperm (r = -0.262, P < 0.01), but positively with pre-freeze sperm concentration (r = 0.247, P < 0.01), and it was significantly higher in the 6-day abstinence group ([70.2 +/- 5.4]%) than in the other abstinence groups (P < 0.01), so was it in the normal sperm morphology rate > 20% group ([71.4 +/- 5.1]%) than in the others (P < 0.01). The survival rate of the post-thaw sperm was not correlated with seasons, blood types, and semen volume (P > 0.05).

CONCLUSIONSperm motility, concentration and morphology and the abstinence period of sperm donors may be valuable predictors of the cryosurvival rate of post-thaw sperm, but no correlation was found between the survival rate and seasons, blood types and semen volume.

Adult ; Cryopreservation ; Humans ; Male ; Retrospective Studies ; Semen Preservation ; Sperm Motility ; Spermatozoa ; Young Adult

OBJECTIVETo formulate a comprehensive treatment program for rheumatoid arthritis arthralgia by clinical observing the efficacy of Xiaoyan Zhitong Paste (XZP).

METHODSAdopted was stratified, block randomized, double-blinded, placebo parallel controlled method. Subjects were assigned to the treatment group and the placebo group. Those in the treatment group were treated by external application of XZP, one to two pastes each time, covering the painful area, exchange once per 24 h, with one-day interval during a 7-day consecutive medication, two 7-days of treatment consisting of one therapeutic course. XZP placebos were applied for those in the placebo group in the same medication way. Joint pain and VAS were taken as main indices for observing the clinical efficacy of XZP.

RESULTSThe improvement of the analgesic effect and the Chinese medical syndrome efficacy of XZP were superior to that of the placebo.

CONCLUSIONXZP showed obvious effect in treating rheumatoid arthritis arthralgia with no obvious adverse reaction.

Adult ; Arthralgia ; drug therapy ; Arthritis, Rheumatoid ; drug therapy ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy ; methods

OBJECTIVETo understand the reproductive health status of female workers in pharmaceutical industry of Gansu Province, to explore influencing factors, and to propose some reference basis of intervening measures.

METHODSThe cluster sampling method was used to study 1801 female workers from 16 pharmaceutical industries in 6 cities (Pingliang, Qingyang, Lanzhou, Dingxi, Zhangye and Jiuquan cities) of Gansu Province. The investigation was performed by interviewing and adopting questionnaires.

RESULTSThere were the problems of labor and organization, which included the overtime work, continuous work, standing for long periods, rapid monotonous action assignments, the loading work and a variety of harmful factors in the working environment of the pharmaceutical industry in Gansu Province. There were many problems in the reproductive health status of female workers. The morbidities of abnormal menstruation and breast diseases in female workers were 43.25% and 20.43%. The order of high morbidities was hyperplasia of mammary glands (91.30%), breast adenofibroma (5.43%) and mastitis (2.99%). The order of morbidities for three reproductive system disease was adnexitis (21.57%), cervical erosion (20.06%) and vaginitis (11.09%). The rates of abnormal menstrual cycle, abnormal menstrual amount and cervical erosion increased with the length of service (P < 0.01). The taking breaks, long standing, loading work, exposure to harmful factors were related to abnormal menstruation (P < 0.05). The rapid repeat monotonous action was an important influencing factor for female reproductive system disease (OR = 1.255, 95%CI = 1.031 ∼ 1.528).

CONCLUSIONThere are relatively serious occupational hazards in the pharmaceutical industry of Gansu Province. The reproductive health status of female workers is not improved. Social public should pay attention to the protection for female workers.

Adolescent ; Adult ; China ; Drug Industry ; Female ; Health Status ; Humans ; Middle Aged ; Occupational Exposure ; Reproductive Health ; Surveys and Questionnaires ; Workplace ; Young Adult

The phyA(m) gene encoding acid phytase and optimized neutral phytase phyCs gene were inserted into expression vector pPIC9K in correct orientation and transformed into Pichia pastoris in order to expand the pH profile of phytase and decrease the cost of production. The fusion phytase phyA(m)-phyCs gene was successfully overexpressed in P. pastoris as an active and extracellular phytase. The yield of total extracellular fusion phytase activity is (25.4+/-0.53) U/ml at the flask scale and (159.1+/-2.92) U/ml for high cell-density fermentation, respectively. Purified fusion phytase exhibits an optimal temperature at 55 degrees C and an optimal pH at 5.5~6.0 and its relative activity remains at a relatively high level of above 70% in the range of pH 2.0 to 7.0. About 51% to 63% of its original activity remains after incubation at 75 degrees C to 95 degrees C for 10 min. Due to heavy glycosylation, the expressed fusion phytase shows a broad and diffuse band in SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis). After deglycosylation by endoglycosidase H (EndoH(f)), the enzyme has an apparent molecular size of 95 kDa. The characterization of the fusion phytase was compared with those of phyCs and phyA(m).
6-Phytase ; genetics ; isolation & purification ; metabolism ; Amino Acid Sequence ; Fermentation ; Genetic Vectors ; Molecular Sequence Data ; Pichia ; genetics ; Recombinant Fusion Proteins ; biosynthesis ; isolation & purification