ObjectiveTo optimize the processing technology of honey bran-fried Rosae Laevigatae Fructus（h-RLF）， formulate relevant quality standards， and explore its improving effect and mechanism on mice with ulcerative colitis（UC） induced by dextran sodium sulfate（DSS）. MethodsTaking the content of polysaccharides and water-soluble extract as the indexes， L₉（3⁴） orthogonal test was used to optimize parameters of the amount of honey bran， frying time and frying temperature. The quality of 15 batches of h-RLF decoction pieces was evaluated according to the optimized process， and the inspection limit standard was preliminarily drawn up. Eighty SPF male Kunming mice were randomly divided into 8 groups， including the blank group， model group， mesalazine group（0.13 g·kg^-1）， RLF group（3.77 g·kg^-1）， bran-fried RLF group（3.77 g·kg^-1）， h-RLF low， medium and high dose groups（1.89， 3.77， 7.54 g·kg^-1）， with 10 mice in each group. The mice in the blank group were free to drink pure water， and the other groups were free to drink 3% DSS solution for 7 days to prepare UC mouse model. Each treatment group was given corresponding drugs by intragastric administration， and the blank and model groups were given equal volume of normal saline. The body weight of mice was recorded daily and the disease activity index（DAI） was calculated. After the administration， the colon tissues of mice were collected to observe the pathological changes by hematoxylin-eosin（HE） staining. The levels of tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6 and IL-10 in the colon of mice were detected by enzyme-linked immunosorbent assay（ELISA）. Western blot was used to detect the expression levels of phosphorylation nuclear transcription factor-κB p65（p-NF-κB p65）， Toll-like receptor 4（TLR4）， p-p38 mitogen-activated protein kinase（p-p38 MAPK）， p-extracellular signal-regulated kinase（p-ERK） and p-c-Jun N-terminal kinase（p-JNK） proteins in colon tissues. ResultsThe optimum processing technology of h-RLF was 20 g honey bran per 100 g RLF， and stir-frying at 200 ℃ for 8 min. The limit standard under the examination of h-RLF was preliminarily formulated as follows：the polysaccharide content should not be less than 25% based on anhydrous glucose（C₆H₁₂O₆）， the content of water-soluble extract should not be less than 38%， the moisture content should not be more than 12.0%， the total ash content should not be more than 5.0%， and the acid-insoluble ash content should not be more than 1.0%. The cluster heat map analysis showed that the quality of RLF from Huanggang， Hubei province was better. Animal experiments showed that compared with the blank group， the DAI score of the model group was significantly increased， the levels of TNF-α， IL-1β and IL-6 in the colon tissue were significantly increased， the IL-10 level was significantly decreased， the colonic mucosa was seriously damaged， accompanied by a large number of inflammatory cell infiltration， tissue congestion and a significant reduction in glands， and the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins were significantly increased（P<0.01）. Compared with the model group， each administration group could alleviate the symptoms of colonic ulcer， the structure of colonic crypt was basically intact， and the glands were arranged in an orderly manner. Among them， the high-dose group of h-RLF had a better effect， which could significantly reduce the DAI score and the levels of TNF-α， IL-1β and IL-6 in colon tissue（P<0.01）， and significantly increase the level of IL-10（P<0.01）， alleviate the colonic mucosal injury， and effectively inhibit the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins（P<0.01）. ConclusionThe key parameters of the processing technology of h-RLF are determined， and the optimized technology is stable and feasible. The established quality standard is simple and reliable， and can be used for the quality control. h-RLF can effectively alleviate DSS-induced UC， and its mechanism may be related to inhibiting the activation of NF-κB/TLR4/MAPK pathway.

Objective To explore the effect of the knockdown of transmembrane 9 superfamily protein member 2 (TM9SF2) on the replication of vesicular stomatitis virus (VSV), and investigate its role in the mechanism of antiviral innate immunity. Methods Small interfering RNA (siRNA) was used to knock down the TM9SF2 gene in human non-small cell lung cancer A549 cells. The CCK-8 method was used to assess cell proliferation. A VSV-green fluorescent protein (VSV-GFP) infected cell model was established. The plaque assay was used to measure the viral titer in the supernatant. RT-qPCR and Western blotting were employed to quantify the mRNA and protein levels of VSV genome replication in A549 cells following VSV infection, as well as the expression of interferon β (IFN-β) mRNA and interferon regulatory factor 3 (IRF3) protein phosphorylation following polyinosinic-polycytidylic acid (poly(I:C)) stimulation. Results Compared to the negative control, the knockdown of TM9SF2 exhibited a significant effect, with no observed impact on A549 cell proliferation. The VSV-GFP infected A549 cell model was successfully established. After viral stimulation, fluorescence intensity was reduced following TM9SF2 knockdown, and the mRNA and protein levels of VSV were significantly downregulated. The viral titer of VSV was decreased. After poly(I:C) stimulation, TM9SF2 knockdown significantly upregulated the mRNA level of IFN-β and the phosphorylation level of IRF3 protein. Conclusion The knockdown of TM9SF2 inhibits the replication of vesicular stomatitis virus, and positively regulates the type I interferon signaling pathway, thus enhancing the host's antiviral innate immune response.
Humans ; Virus Replication/genetics* ; Signal Transduction ; Membrane Proteins/metabolism* ; A549 Cells ; Vesiculovirus/physiology* ; Interferon-beta/metabolism* ; Interferon Regulatory Factor-3/genetics* ; Interferon Type I/metabolism* ; Vesicular Stomatitis/immunology* ; Gene Knockdown Techniques ; Vesicular stomatitis Indiana virus/physiology* ; RNA, Small Interfering/genetics*

In order to standardize the clinical diagnosis and treatment of upper airway cough syndrome (UACS) for children in China, Dongzhimen Hospital of Beijing University of Chinese Medicine and Affiliated Hospital of Liaoning University of Traditional Chinese Medicine initiated the development of this Traditional Chinese Medicine Diagnosis and Treatment Guidelines for Children with Upper Airway cough Syndrome based on evidence-based medical evidence. This guideline will process registration, write a plan, and develop relevant processes and writing norms, develop and publish official documents. This plan mainly introduces the scope of the guidelines, the purpose and significance, the composition of the guidelines working group, the management of conflicts of interest, the collection, selection and determination of clinical problems, the retrieval, screening and rating of evidence, and the consensus of recommendations. Registration information: This study has been registered in the international practice guidelines registry platform with the registration code of PREPARE-2023CN087.

Objective To design a pH-sensitive nintedanib liposomes(Nb-Lips)which targeted the acidic microenvironment of pulmonary fibrosis.The entrapment efficiency(EE%)was optimized by the formulation process.Methods Nintedanib liposomes were prepared by membrane hydration method,and the formulation of nintedanib liposomes were optimized by single factor experiments and response surface method(RSM).The particle size,polymer dispersity index(PDI),Zeta potential and encapsulation rate was investigated by dynamic light scattering technique and microcolumn centrifugation method.The release behavior of nintedanib liposomes in artificial lung fluid with pH 7.4 and artificial lung fluid with pH 5.3 was investigated by dialysis method.Nintedanib liposomes were atomized with a compressed air atomizer and its atomization stability and aerodynamic particle size were investigated.Results The particle size of nintedanib liposomes was(100.651±7.315)nm,the PDI was(0.328±0.026),the zeta potential was(21.633±2.004)mV,and the encapsulation rate was higher than 80%.Compared with nintedanib solution at pH 7.4,the total release of nintedanib liposomes in pH 5.3 artificial lung solution was 60.78%higher,and the release of nintedanib liposomes in pH 5.3 artificial lung solution was 48h delayed,which was much higher than that of nintedanib solution.The data reveals no significant differences in particle size,potential and PDI before and after atomization of nintedanib liposomes,and the encapsulation rate decreased 4.25%.The fine particle fraction of the atomized droplets was 37.49%.Conclusion The response surface method can effectively improve the encapsulation rate of nintedanib liposomes,and successfully prepare nintedanib liposomes that are sensitive to acidic environment,and can be inhaled and released slowly.

Closed-loop hospital management can effectivly cope with the COVID-19 pandemic. In order to ensure the continuity of treatments for hemodialysis patients under closed-loop management and minimize possible medical and infection risks, Huashan Hospital affiliated to Fudan University and 9 hospitals in Shanghai established a hemodialysis alliance in January 2021.The alliance optimized hemodialysis resources within the region through overall planning by preparing sites, materials and personnel shifts in advance, and establishing management systems and work processes to ensure that patients could be quickly and orderly diverted to other blood dialysis centers for uninterrupted high-quality hemodialysis services, in case that some hemodialysis centers in the alliance under closed-loop management.From November 2021 to April 2022, 317 of 1 459 hemodialysis patients in the alliance were diverted to other centers for treatment, accumulating 1 215 times/cases of treatments without obvious adverse reactions. The practice could provide a reference for medical institutions to quickly establish mutual support mode under major public health events.

Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.

Objective:To investigate the clinical significance and correlation of arginase 1 (Arg-1) and inducible nitric oxide synthase (iNOS) expression in hepatocellular carcinoma (HCC).Methods:The expression of Arg-1and iNOS in 146 cases of hepatocellular carcinoma tissues and corresponding adjacent tissues was detected by immunohistochemistry. The clinicopathological characteristics and the correlation between the expressions and prognosis were determined by chi square test, Spearman’s rank correlation, Kaplan-Meier survival analysis and Cox regression analysis.Results:The positive rates of Arg-1 and iNOS were 18.7% (23/123) and 37.0% (54/146), respectively, which was significantly lower than the adjacent tissues [100%(146/146) and 93.8% (137/146)] and the difference was statistically significant ( χ2 = 212.521, P < 0.01, χ2 = 104.276, P < 0.01). There was a positive correlation between the both expression ( r = 0.331, P < 0.01). Arg-1 low expression was correlated with preoperative serum alpha-fetoprotein (AFP) level, tumor size, differentiation degree, histological types and Edmondson’s grade. iNOS low expression was correlated with the differentiation degree and Edmondson’s grade ( P < 0.05). Kaplan Meier survival analysis showed that in patients with recurrence-free survival (RFs), Arg-1 (+) group > Arg-1 (-) group and Arg-1 (+) iNOS (+) group > Arg-1 (+) iNOS (-) group > Arg-1 (-) iNOS (-) group ( P < 0.05). Cox multivariate analysis showed that age, tumor size, Edmondson’s grade, vascular tumor emboli were significantly correlated with RFs ( P < 0.05). Conclusion:There is a positive correlation between Arg-1 and iNOS expressions in HCC, and both may reflect the HCC malignant degree. The reduced/absent expression of both may participate in the occurrence and development of HCC. The combined detection of Arg-1 and iNOS on HCC may have certain significance for the judgment of differentiation degree and prognosis.

Objective: To understand the serum levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (T3), and thyroxine (T4) and identify the related influencing factors of thyroid dysfunction in drug users. Methods: From June to August 2018, a face-to-face questionnaire survey was conducted in 788 male drug users in a drug rehabilitation center in Jiangsu province to collect their socio-demographic information. Then, venous blood sample was collected from each participant for the detection of various hematological indicators, such as thyroid hormones. Results: The abnormal rates of T3, T4, FT3, FT4 and TSH were 4.57%, 1.27%, 0.51%, 0.38% and 0.89%, respectively, in the male drug users. HCV infection was an influencing factor for abnormal T3 level in the male drug users (OR=8.52, 95%CI: 2.36-30.74, P=0.001). And serum T3 (P<0.001) and T4 (P=0.048) levels increased with increasing HCV viral load. Conclusions HCV infection was an influencing factor for the abnormality of serum T3 level in drug users. Therefore, thyroid-related knowledge should be added in the health education for drug users, and the monitoring of thyroid function should be strengthened for drug users infected with HCV.

Objective To evaluate the effect of dexmedimidine on intestinal injury in rats with endotoxemia.Methods Twenty-four healthy adult male Sprague-Dawley rats,aged 2-3 months,weighing 200-250 g,were divided into 4 groups (n =6 each) using a random number table method:control group (group C),endotoxemia group (group E),dexmedimidine group (group D) and dexmedimidine plus α7 subunit-containing nicotinic acetylcholine receptor antagonist group (D +α-BGT group).The endotoxemia model was established by injecting lipopolysaccharide (LPS) 10 mg/kg via the femoral vein.Dexmedetomidine 40 μg/kg was injected and 15 min later LPS was intravenously injected in group D.Dexmedetomidine 40 μg/kg was intraperitoneally injected after intraperitoneal injection of α-bungarotoxin 1 μg/kg,and 15 min later LPS was intravenously injected in group D+o-BGT.Blood samples were collected from the abdominal aorta at 6 h after LPS injection for determination of the plasma interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations (by enzyme-linked immunosorbent assay).Rats were sacrificed after blood sampling,and intestinal tissues were obtained for examination of the pathological changes and for determination of the myeloperoxidase (MPO) activity (by chemical colorimetry) and expression of NF-κB p65 in nucleoprotein (by Western blot).Results Compared with group C,the plasma IL-6 and TNF-o concentrations and MPO activity in intestinal tissues were significantly increased,and the expression of NF-κB p65 in nucleoprotein was up-regulated in the other 3 groups (P＜0.05).Compared with group E,the plasma IL-6 and TNF-α concentrations and MPO activity in intestinal tissues were significantly decreased,the expression of NF-κB p65 in nucleoprotein was down-regulated (p＜0.05),and the pathological changes of intestinal tissues were significantly attenuated in group D.Compared with group D,the plasma IL-6 and TNF-α concentrations and MPO activity in intestinal tissues were significantly increased,the expression of NF-κB p65 in nucleoprotein was up-regulated (P＜0.05),and the pathological changes of intestinal tissues were accentuated in group D+α-BGT.Conclusion Dexmedetomidine can reduce the intestinal injury in rats with endotoxemia,and the mechanism may be related to activating cholinergic anti-inflammatory pathway and further inhibiting inflammatory responses.

Objective To investigate the high risk factors for wheezing of low birth weight premature infants with wheezing.Methods A cohort study of 143 premature infants,whose gestation less than 37 weeks and birth weight less than 2 500 g,were collected from Neonatal Intensive Care Unit of Kunming Children's Hospital,from December 2012 to November 2013.Follow-up investigation was conducted,and those with wheezing were enrolled in the study.Many possible factors causing wheezing were analyzed,such as general conditions in the neonatal period,family conditions,and treatment.SPSS 17.0 statistical software was used to analyze the data.Single factor analysis was used by x2 test and rank sum test to evaluate the possible risk factors.Multiple factors analysis was made by Logistic regression analysis.P ＜ 0.05 was viewed as having statistical difference.Results (1) The risk factors for wheezing in the premature infants were:continuous positive airway pressure (CPAP) noninvasive ventilation (x2 =8.531,P =0.003),ventilation (x2 =4.800,P =0.028),caesarean section (x2 =6.787,P =0.009),the use of pulmonary surfactant (x2 =5.455,P =0.020),using antibiotics used at hospital (x2 =5.192,P =0.023),father smoking(x2 =5.406,P =0.020),maternal smoking (x2 =8.531,P =0.003),maternal allergic history (x2 =8.297,P =0.004),compatriot history of allergies (x2 =8.297,P =0.004) or asthma (x2 =9.774,P =0.002),family environment with dust and excitant gas (x2 =12.831,P =0.000) were the risk factors for the wheezing in the low birth weight premature infants.(2)Multi-factor classification Logistic regression analysis showed that CPAP (OR =58.414,95 ％ CI:3.317-1 028.646,P =0.005),mother smoking during pregnancy (OR =11.953,95 ％ CI:1.309-109.120,P =0.028),compatriot history of allergies (OR=135.769,95％ CI:4.914-3 751.419,P =0.004),family environment(OR =83.738,95％ CI:4.416-1 587.982,P =0.003),were independent risk factors for wheezing in low birth weight premature infants;natural labor was protective factor for wheezing in low birth weight premature infants (OR =0.045,95％ CI:0.004-0.574,P =0.017).(3)The sensitivity and specificity of risk factors were analyzed.The highest sensitivity was estimated for the father's history of allergy(83.3％).The highest specificity was estimated for the use of antibiotics at hospital (76.7％).Conclusions The study shows that CPAP noninvasive ventilation,mother smoking during pregnancy,allergy history of their brothers and sisters,family environment with dust and excitant gas are independent risk factors for wheezing in the low birth weight premature infants.There is no single risk factor with both high sensitivity and high specificity.