OBJECTIVES: To study the molecular mechanisms of LDH-loaded si-NEAT1 for regulating paclitaxel resistance and tumor-associated macrophage (TAM) polarization in breast cancer. METHODS: qRT-PCR and Western blotting were used to detect the expression of lncRNA NEAT1, miR-133b, and PD-L1 in breast cancer SKBR3 cells and paclitaxel-resistant SKBR3 cells (SKBR3-PR). The effects of transfection with si-NEAT1 and miR-133b mimics on MRP, MCRP and PD-L1 expressions and cell proliferation, migration and apoptosis were investigated using qRT-PCR, Western blotting, scratch and Transwell assays, and flow cytometry. Rescue experiments were conducted using si-NEAT1 and miR-133b inhibitor. Human THP-1 macrophages were cultured in the presence of conditioned media (CM) derived from SKBR3 and SKBR3-PR cells with or with si-NEAT1 transfection for comparison of IL-4-induced macrophage polarization by detecting the surface markers. LDH@si-NEAT1 nanocarriers were constructed, and their effects on MRP, MCRP and PD-L1 expressions and cell behaviors of the tumor cells were examined. THP-1 cells were treated with the CM from LDH@si-NEAT1-treated tumor cells, and the changes in their polarization were assessed. RESULTS: SKBR3-PR cells showered significantly upregulated NEAT1 and PD-L1 expressions and lowered miR-133b expression as compared with their parental cells. Transfection with si-NEAT1 and miR-133b mimics inhibited viability, promoted apoptosis and enhanced MRP and BCRP expressions in SKBR3-PR cells. NEAT1 knockdown obvious upregulated miR-133b and downregulated PD-L1, MRP and BCRP expressions. The CM from SKBR3-PR cells obviously promoted M2 polarization of THP-1 macrophages, which was significantly inhibited by CM from si-NEAT1-transfected cells. Treatment with LDH@si-NEAT1 effectively inhibited migration and invasion, promoted apoptosis, and reduced MRP, BCRP and PD-L1 expressions in the tumor cells. The CM from LDH@si-NEAT1-treated SKBR3-PR cells significantly downregulated Arg-1, CD163, IL-10, and PD-L1 and upregulated miR-133b expression in THP-1 macrophages. CONCLUSIONS LDH@si-NEAT1 reduces paclitaxel resistance of breast cancer cells and inhibits TAM polarization by targeting the miR-133b/PD-L1 axis.
Humans ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; Paclitaxel/pharmacology* ; Breast Neoplasms/metabolism* ; Drug Resistance, Neoplasm ; B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Female ; Tumor-Associated Macrophages ; Apoptosis ; Cell Proliferation ; Macrophages ; Cell Movement

Five new flavan-4-ol glycosides jixueqiosides A-E (1-5) and two new flavan glycosides jixueqiosides F and G (6 and 7), along with twelve known flavan-4-ol glycosides (8-19), were isolated from the roots of Pronephrium penangianum. Comprehensive spectral analyses, X-ray single-crystal diffraction, and theoretical electronic circular dichroism (ECD) calculations established structures and absolute configurations. A single crystal structure of flavan-4-ol glycoside (14) was reported for the first time, while the characteristic ECD and NMR data for all isolated flavan-4-ol glycosides (1-5 , 8-19) were analyzed, establishing a set of empirical rules. Activity screening of these isolates showed that 8 and 9 could inhibit the proliferation of MDA-MB-231 and MCF-7 cells with IC₅₀ values of 7.93 ? 2.85 ?mol?L^-1 and 5.87 ? 1.58 ?mol?L^-1 (MDA-MB-231), and 2.21 ? 1.38 ?mol?L^-1 and 3.52 ? 1.55 ?mol?L^-1 (MCF-7), respectively. Western blotting and flow cytometry analyses demonstrated that 8 and 9 dose-dependently induced apoptosis in MDA-MB-231 cells by up-regulating BAX, activating caspase-3 and down-regulating BCL-2. Additionally, compound 8 affected autophagy-related proteins, increasing the ratio of LC3-II/LC3-I and Beclin-1 levels to inhibit MDA-MB-231 cell proliferation. Moreover, anti-inflammatory studies indicated that 2, 3, 7, 13, 14, and 18 moderately inhibited tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and nitric oxide (NO) release.
Humans ; Plant Roots/chemistry* ; Glycosides/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Flavonoids/isolation & purification* ; Cell Proliferation/drug effects* ; Antineoplastic Agents, Phytogenic/isolation & purification* ; Molecular Structure ; Apoptosis/drug effects* ; Cell Line, Tumor ; Tumor Necrosis Factor-alpha/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Interleukin-6/immunology* ; Animals ; Mice

OBJECTIVE To investigate the effect of polymorphisms of solute carrier organic anion transporter family, member 1B3(SLCO1B3) gene on the pharmacodynamics of mycophenolate mofetil(MMF) in patients with lupus nephritis. METHODS Patients with lupus nephritis who were treated in Jieyang People’s Hospital from September 2019 to April 2021 were selected. All subjects were treated with MMF for at least 12 months, or discontinued due to poor efficacy. The efficacy of MMF was evaluated. The SLCO1B3 334T>G/699G>A(rs4149117/rs7311358) genotype was detected using Agena MassARRAY®, and the correlation between gene polymorphisms and MMF pharmacodynamics was analyzed using SPSS 25.0 software. RESULTS The genotype frequencies of SLCO1B3 334T>G/699G>A were in Hardy-Weinberg equilibrium. The probability of poor MMF treatment effect of 334GG/699AA carriers was significantly higher than that of 334TT/699AA and 334TG/699GA carriers(P<0.001); Logistic regression showed that both 334GG/699AA and urine protein>2.5 g·(24 h)−1 were the risk factors for poor MMF treatment[OR=4.038(1.731, 9.420), P<0.001; OR=4.157(1.705, 10.137), P=0.002]. Combined analysis showed that patients with both 334GG/699AA genotype and urine protein>2.5 g·(24 h)−1 were at higher risk for poor efficacy[OR=8.563(3.301, 22.216), P<0.001]. CONCLUSION SLCO1B3 334T>G/699G>A is related to the efficacy of MMF treating lupus nephritis, and 334GG/699AA carriers are more likely to result in poor efficacy.

Humans ; Asthma/drug therapy* ; Biological Therapy

Objective:To analyze the therapeutic effect of adding interleukin (IL)-4Rα monoclonal antibody (duplizumab) to patients with multiple types of inflammatory diseases.Methods:Six patients with multiple types of inflammatory diseases who started to use duplizumab from August 2020 were enrolled. The changes of airway inflammation, lung function, sinuses computed tomography (CT), Asthma Control Questionnaire-5 (ACQ-5), Sino-Nasal Outcome Test-22 (SNOT-22), Pennsylvania Smell Identification Test (UPSIT) and Numerical Rating Scale (NRS) score before and after duplizumab treatment were retrospectively analyzed. All patients were treated with doprilumab for more than 5 months.Results:4 of the 6 patients had both severe asthma and chronic sinusitis, and 2 patients had both severe asthma, chronic sinusitis and atopic dermatitis. After treatment, the pulmonary function of 6 patients was improved, the levels of sputum eosinophils, exhaled nitric oxide and total IgE were decreased (all P<0.05), and the scores of paranasal sinus CT, ACQ-5, SNOT-22 and UPSIT were significantly improved (all P<0.05). However, 3 patients had increased peripheral blood eosinophils during the treatment. Conclusions:Duplizumab is effective for a variety of type 2 inflammatory diseases without obvious adverse reactions, and the peripheral eosinophils may increase during the treatment.

Objective:To explore the application effect of quantitative exercise nursing intervention based on WeChat platform in the recovery of patients with lower extremity arteriosclerosis obliterans.Methods:A total of 128 patients with lower extremity arteriosclerosis obliterans who were treated in Department of Vascular Surgery of the First Affiliated Hospital of Zhengzhou University were selected from June 2019 to February 2021. They were randomly divided into the control group and the observation group, with 64 cases in each group. The control group used routine nursing, while the observation group used the quantitative exercise nursing intervention based on the WeChat platform. Ankle-brachial index (ABI) and walking ability [Walking Impairment Questionnaire (WIQ) ] were compared between the two groups. The quality of life and nursing satisfaction of patients in two groups were investigated by World Health Organization Quality of Life Assessment Brief Scale (WHOQOL-BREF) and Newcastle Satisfaction with Nursing Scale (NSNS) .Results:After the intervention, scores of ABI, WIQ, WHOQOL-BREF and nursing satisfaction of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Quantitative exercise nursing intervention based on the WeChat platform can promote the functional rehabilitation of patients with lower extremity arteriosclerosis obliterans and improve quality of life and satisfaction of patients, which is worthy of clinical application.

OBJECTIVE： To prepare the Peppermint oil moisturizing microemulsion for nasal mucosa and survey its mucosal adhesion and cilia toxicity. METHODS： The polyoxyethylene hydrogenated castor oil was used as emulsifier to prepare the Peppermint oil moisturizing microemulsion for nasal mucosa， and the preparation technology was optimized on the basis of comprehensive score by orthogonal design. The microemulsion was characterized and the menthol content was determined by GC. The mucosal adhesion was evaluated by measuring the transport rate by cilia in vivo， and the cilia toxicity of microemulsion was evaluated by measuring the sustained movement time of cilia in vitro. RESULTS： The optimal preparation technology of self-made microemulsion was to firstly disperse the peppermint oil and the emulsifier， then add anhydrous ethanol， edible glycerin and distilled water， and stir at 1 200 r/min for 2 h. The average contents of menthol in the three batches of the microemulsion were 2.682， 2.507 and 2.496 mg/mL （RSD＝2.89％，n＝3）， respectively. The cilia transport rates in vivo were （0.65±0.01）， （0.78±0.03）and （0.92±0.04） cm/min in high-dose， medium-dose， and low-dose groups of self-made microemulsion （2.561， 0.256， 0.128 mg/mL of menthol） respectively， which were significantly lower than normal saline group and compound menthol nasal droups （P＜0.05）. The cilia movement time in vitro were（206.7±4.9）， （226.0±13.5）， （269.3±12.9）min， which were significantly longer than sodium deoxycholate group （P＜0.05）. CONCLUSIONS： The preparation technology of self-made microemulsion is easy-to-handle and controllable in quality. The prepared microemulsion shows good mucosal adhesion without cilia toxicity．

Allergic rhinitis (AR) is a global health problem that causes major illnesses and disabilities worldwide. Epidemiologic studies have demonstrated that the prevalence of AR has increased progressively over the last few decades in more developed countries and currently affects up to 40% of the population worldwide. Likewise, a rising trend of AR has also been observed over the last 2–3 decades in developing countries including China, with the prevalence of AR varying widely in these countries. A survey of self-reported AR over a 6-year period in the general Chinese adult population reported that the standardized prevalence of adult AR increased from 11.1% in 2005 to 17.6% in 2011. An increasing number of original articles and imporclinical trials on the epidemiology, pathophysiologic mechanisms, diagnosis, management and comorbidities of AR in Chinese subjects have been published in international peer-reviewed journals over the past 2 decades, and substantially added to our understanding of this disease as a global problem. Although guidelines for the diagnosis and treatment of AR in Chinese subjects have also been published, they have not been translated into English and therefore not generally accessible for reference to non-Chinese speaking international medical communities. Moreover, methods for the diagnosis and treatment of AR in China have not been standardized entirely and some patients are still treated according to regional preferences. Thus, the present guidelines have been developed by the Chinese Society of Allergy to be accessible to both national and international medical communities involved in the management of AR patients. These guidelines have been prepared in line with existing international guidelines to provide evidence-based recommendations for the diagnosis and management of AR in China.
Adult ; Asian Continental Ancestry Group* ; China ; Comorbidity ; Developed Countries ; Developing Countries ; Diagnosis* ; Epidemiologic Studies ; Epidemiology ; Global Health ; Humans ; Hypersensitivity* ; Prevalence ; Rhinitis, Allergic*

Objective To explore the risk factors ,prevention and treatment of the occurrence of perirenal hematoma after flexible lithotripsy. Methods We retrospectively analyzed the clinical data of 18 patients with symptomatic perirenal hematoma from 1259 who had undergone ureteral flexible lithotripsy in our hospital during the period of April 2007 to April 2016. Of the 18 patients,7 were complicated with diabetes mellitus,11 had urinary tract infection;15 were female,and 3 were male. Results Perirenal hematoma was confirmed by B ultrasound and CT,which situated on the Posterolateral side of the kidney in 8 patients,and on the lower pole and abdominal side in 10. Hematoma depth was 2.6-15.3 cm(average was 5.2 cm). The hematoma?related symptoms gradually disappeared in 11 patients 7 to 14 days after they received conservative treatment. 5 recovered gradually 15 days after undergoing hematoma puncture and drainage ,and 2 recovered 36 days after receiving open surgery for removal of hematoma. Conclusions Female,diabetes,urinary tract infection,bigger stone size,prolonged surgical duration,and infected stones were the risk factors for perinephric hematoma related to ureteroscopic lithotripsy. Full preoperative preparation ,effective anti?infection ,intraoperative improvement of calculus?breaking skills and use of large caliber semirigid through sheath,low pressure perfusion,shorter surgical duration,and staging surgery are effective ways to reduce the occurrence of perirenal hematoma.

Objective To evaluate the clinical value of hs-CRP,Tbil and BUA in the diagnosis of coronary atherosclerosis on 320 slice dynamic volume computed tomography(320-DVCT).Methods 160 patients with stable angina pectoris were included.All patients underwent 320-DVCT coronary artery imaging and laboratory testing including plasma hs-CRP,Tbil and BUA.The plaques of coronary artery were classified as soft plaque,fibrous plaque and calcified plaque on CT values.The three indicators were used to confirm the ability of diagnosis on number of lesions,plaque character and the degree of stenosis.100 healthy persons served as the control group.Results With the concentration of hs-CRP,BUA increased and Tbil concentration decreased,the number and the stenosis degree of coronary lesions became increased,and easier to form a soft plaque.Conclusion The hs CRP,Tbil and BUA can offer the accurate diagnosis of lesions number,plaque character and stenosis degree of the coronary artery,which is showed on 320-DVCT.The hs-CRP,Tbil and BUA are conducive to the risk assessment of coronary atherosclerosis.