OBJECTIVE: To determine the effects of berberine (BBR) on the activation of toll-like receptor 4 (TLR4), nuclear factor (NF)κB (NF-κB) signaling and NLRP3 inflammasome in patients with gout. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from 24 acute (AP) and 41 non-acute (NAP) phases of primary gout patients, respectively, as well as 30 healthy controls (HC). TLR4, NF-κB (p65), NLRP3, apoptosis-associated specklike protein containing a CARD (PYCARD), cysteinyl aspartate specific proteinase-1 (CASP1), and interleukin-1β (IL-1β) mRNA expression levels in PBMCs were measured by quantitative reverse transcriptase polymerase chain reaction. The protein levels of TLR4, myeloid differentiation factor 88 (MyD88), NF-κB (p50/65), inhibitor of kappa B kinase α/β (IKKα/β), NF-κB inhibitor α (IKBα), phospho-IKKα/β (p-IKKα/β), NLRP3, PYCARD, and CASP1 were monitored by Western blotting. Serum IL-1β protein level was measured using enzyme-linked immunosorbent assay (ELISA). In addition, PBMCs from HC and macrophages derived from a spontaneously immortalized monocyte-like cell line (THP-1) were stimulated using monosodium urate (MSU, 100 µg/mL), 0.1% dimethyl sulfoxide, 25 µmol/L BBR, and 10, 25, and 50 µmol/L BBR+100 µg/mL MSU for different time periods. The protein levels of IL-1β and IL-18 in cell culture supernatants was measured by ELISA, and the protein expressions of TLR4, MyD88, NF-κB (p50/p65), IKKα/β, I κBβ, p-IKKα/β, NLRP3, PYCARD, and CASP1 in macrophages were analyzed by Western blotting. RESULTS: (1) TLR4, NF-κB (p65), PYCARD, CASP1, and IL-1β mRNA levels in PBMCs were significantly higher in the AP group than in the HC group (P<0.05). The NLRP3 mRNA expression levels in PBMCs were found to be significantly lower in the AP and NAP groups than in the HC group (P<0.05, P<0.01). (2) The protein levels of TLR4, IKKβ, MyD88, NF-κB, p-IKKα/β, PYCARD, and CASP1 in PBMCs were significantly higher, and those of IκBα, IKKα, and NLRP3 were found to be significantly lower in the AP group than in the HC group (P<0.05 or P<0.01). (3) The serum IL-1β protein levels were significantly higher in the AP and NAP groups than in the HC group (P<0.01). (4) The IL-1β protein level was significantly lower in the culture supernatants of the PBMCs stimulated with MSU for 3 and 6 h in the 25 and 50 µmoL/L BBR groups compared with that in the MSU group (P<0.01). (5) The protein levels of IL-1β and IL-18 were also significantly lower in the culture supernatants of macrophages stimulated with MSU for 3 and 6 h in BBR groups compared with those in the MSU group (P<0.01). (6) The protein levels of TLR4, MyD88, NF-κB (p50, p65, p105), IKKα/β, p-IκBα, p-IKKα/β, PYCARD, and CASP1 were significantly differed between the macrophages stimulated with MSU for 0.5 and 6 h in BBR groups compared with those in the MSU group (P<0.05 or P<0.01). CONCLUSIONS Activation of TLR4-NFκB signaling and NLRP3 inflammasome by MSU crystals drives the progression of gout inflammation. BBR ameliorates gouty inflammation, which is mechanistically associated with its regulation of TLR4-NF-κB signaling and NLRP3 inflammasome expression.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

For quantitative analysis of related substances in TSD-1 active pharmaceutical ingredient, structures of prepared impurities were confirmed by NMR and UHPLC-MS, and a high performance liquid chromatographic method was established to determine the related substances in TSD-1. The analytical column was an Agilent ZORBAX Eclipe XDB-C8 (250 mm × 4.6 mm, 5 µm). The mobile phase A was 50 mmol·L^-1 ammonium acetate solution (adjusted pH to 5.8 with acetic acid) and the mobile phase B was acetonitrile. The whole run was carried out by gradient elution at a flow rate of 1.0 mL·min^-1. The detection wavelength was set at 240 nm and the column temperature was 30 ℃. The resolutions among peaks of TSD-1, impurity A, impurity B, TSD-D, and TSD-F were good. The calibration curves (n = 7) of TSD-1, impurity A, impurity B, TSD-D and TSD-F were linear in their respective weight ranges of 0.242-48.4 µg·mL^-1 (r = 1.000 0), 0.244-9.75 µg·mL^-1 (r = 0.999 9), 0.244-4.80 µg·mL^-1 (r = 0.999 9), 0.254-1.02 µg·mL^-1 (r = 0.999 9), and 0.247-0.987 µg·mL^-1 (r = 0.999 9). The lower limits of quantitation were 0.244, 0.244, 0.254, and 0.247 µg·mL^-1 for impurity A, impurity B, TSD-D, and TSD-F, respectively, and the average recovery of each impurity ranged from 99.08% to 103.00% with high accuracy. TSD-D and TSD-F were not detected in the three batches of TSD-1 active pharmaceutical ingredients, and impurity A and impurity B were not detected beyond the limit. The established HPLC method is simple, accurate, and suitable for determination of related substances of TSD-1, which can provide a valuable reference for the subsequent development of TSD-1.

Objective To assess the occupational health risk of noise in a plastic products enterprise and determine the key risk Methods - points. The workplace of a plastic products enterprise and its 388 noise exposed workers were selected as the ， research subjects using a convenient sampling method. The noise intensity in the workplace of the enterprise was measured and - GBZ/T 229.4-2012 the individual noise exposure level and pure tone hearing test were carried out in the noise exposed workers. Classification of Occupational Hazards at Workplaces--Part 4： Occupational Exposure to Noise（ GBZ/T hereinafter referred to as 229.4-2012） - was used to evaluate the hazardous degree of noise in different posts. The risk of high frequency hearing loss （ ） - （ ） - ， ， HFHL and occupational noise induced deafness ONID in noise exposed workers in different posts at 45.0 50.0 55.0 and WS/T 754-2016 Guideline for Risk Management of Occupational Noise Hazard（ 60.0 years of age were predicted using hereinafter WS/T 754-2016）Results referred to as . The noise in the workplace of this plastic product enterprise was found to exceed the - occupational exposure limits with the rate of 46.6%. The maximum level of normalization of equivalent continuous A weighted - （ ） sound pressure level to a nominal 40 h working week of exposure to noise in workers of six posts was 84.0 93.0 dB A . - ， ， ， According to GBZ/T 229.4 2012 the noise hazards of the posts including extrusion premixing unloading and utility - ， maintenance were mild or moderate except for the film and packaging posts. According to WS/T 754 2016 the risks of HFHL in ， ， the film and packaging operators at age ≥50.0 years old were at acceptable risk and the risks of HFHL in operators of extrusion ， ， premixing unloading and utility maintenance at age ≥45.0 years old were at moderate risk or high risk. The risks of ONID for ， the film packaging and utility maintenance operators at age ≥55.0 years old were at acceptable risk or moderate risk. The risksof ONID for extrusion premixing and unloading operators at age ≥50.0 years old were at high risk. Extrusion operators with （ ） exposure to toluene below the occupational exposure limit had a higher risk of HFHL high risk than unloading operators （ ） Conclusion moderate risk at age 45.0 years with the same noise intensity. The noise exposure intensity is high in the ， workplace of the plastic product enterprise. The workers in posts of extrusion premixing and unloading are at high risk levels of HFHL and ONID.

The present study aimed to explore the mechanism of the sweating of Dipsacus asper on content changes of triterpene sa-ponins by detecting the total triterpene saponins and the index component asperosaponin Ⅵ in the crude and sweated D. asper, and analyzing the differentially expressed proteins by isobaric tags for relative and absolute quantification(iTRAQ) combined with LC-MS/MS. After sweating, the content of total triterpene saponins decreased manifestly, while that of asperosaponin Ⅵ increased significantly. As revealed by the iTRAQ-LC-MS/MS analysis, 140 proteins with significant differential expression were figured out, with 50 up-regulated and 90 down-regulated. GO analysis indicated a variety of hydrolases, oxido-reductases, and transferases in the differential proteins. The results of activity test on two differentially expressed oxido-reductases were consistent with those of the iTRAQ-LC-MS/MS analysis. As demonstrated by the analysis of enzymes related to the triterpene saponin biosynthesis pathway, two enzymes(from CYP450 and UGT families, respectively, which are involved in the structural modification of triterpene saponins) were significantly down-regulated after sweating. The findings suggested that sweating of D. asper presumedly regulated triterpene saponins by affecting the expression of downstream CYP450 s and UGTs in the biosynthesis pathway of triterpene saponins of D. asper.
Chromatography, Liquid ; Dipsacaceae ; Humans ; Saponins ; Sweating ; Tandem Mass Spectrometry ; Triterpenes

OBJECTIVE: To investigate the complications of tourniquet in the clinical application of lower tibiofibular fracture. METHODS: From June 2018 to September 2019, 33 cases of closed lower tibiofibular fractures (AO type 43A) were treated with plates and screws and were divided into two groups according to whether pueumatic tourniquet was used:16 cases in the observation group, 13 males and 3 females, aged 18 to 69 (38.8±17.0) years, the operation time after injury was (6.9±1.7) days, and tourniquet was not used during operation. There were 17 cases in the control group, 13 males and 4 females, aged from 21 to 71 (43.8±12.4) years, the operation time after injury was (6.5±1.0) days, automatic pneumatic tourniquetwas routinely used in the operation. The operation time, blood loss, postoperative swelling, pain and other complications were compared between two groups. RESULTS: Total of 33 patients were followed up for an average of 15 months. There was no significant difference in operation time and blood loss between two groups ( CONCLUSION The fracture of lower tibiofibular segment is superficial and easy to be exposed and fixed during operation. In order to avoid tourniquet complications, it is not recommended to use air bag tourniquet routinely or minimize the application time of tourniquet.
Adolescent ; Adult ; Aged ; Female ; Fracture Fixation, Internal ; Fractures, Bone/surgery* ; Humans ; Male ; Middle Aged ; Operative Time ; Retrospective Studies ; Tourniquets ; Treatment Outcome ; Young Adult

Objective: To explore the value of chest CT features and clinical indexes in the differential diagnosis between suspected COVID-19 with two or more negative nucleic acid tests and confirmed COVID-19. Methods: The clinical data and chest CT images of 105 cases withconfirmedCOVID-19 (55 males and 50 females, aged from 2 month to 88 years) and 97 cases with suspected COVID-19(59 males and 38 females, aged from 1 month to 93 years) were analyzed retrospectively in Shiyan Taihe Hospital from January 21 to February 10, 2020. χ²test and two independent sample t test were used to analyze the clinical data and CT signs of the two cases, with P<0.05 for the difference statistically significant. Results: Compared with the suspected patients, the average age of diagnosis of covid-19 was higher (t = 2.460, P = 0.01). The main pathological changes were pure ground glass (68 cases) and mixed ground glass density (53 cases) (χ² = 50.016, P< 0.01). Interstitial thickening (83 cases) (χ² = 55.395, P< 0.01), vascular thickening (73 cases) (χ² = 57.527, P< 0.01), air bronchoscopic sign or bronchiectasis Zhang (67 cases) (χ² = 17.899, P< 0.01), cord focus (54 cases) (χ² = 5.500, P = 0.02), easily distributed under the pleura and the long axis of the lesion was parallel to the pleura (89 cases) (χ² = 23.597, P< 0.01), most of them had no pleural effusion (χ² = 7.017, P< 0.01); both lesions were mainly distributed in patches (89 cases were confirmed, 87 suspected) (χ² = 19.573, P< 0.01). In addition, the lesions of patients with confirmed covid-19 showed progress in short term (72 / 87, 82.76%), and those with suspected covid-19 showed remission in short term (63 / 89, 70.78%). The difference was statistically significant (χ² = 51.114, P< 0.01). There was no significant difference in gender and distribution of pulmonary lobes (χ² = 1.462, P= 0.23; χ² = 7.381, P= 0.19). The number of white blood cells (χ² = 17.891, P< 0.01) and the percentage of lymphocytes (χ² = 11.151,P< 0.01) of covid-19 were mostly normal or decreased, creatine kinase (χ² = 9.589, P< 0.01) were mostly normal, and erythrocyte sedimentation rate was mostly normal or increased (χ² = 4.240, P= 0.04). Conclusions The imaging features and biochemical indexes of diagnosed COVID-19 are different from those of suspected COVID-19. The comparative analysis of imaging features, clinical indexes and reexamination are helpful for the differential diagnosis of COVID-19 and suspected COVID-19.

OBJECTIVE: To clarify whether lycium barbarum polysaccharides (LBP) have protective effects on retina neuronal cells in diabetic rats and to identify the related mechanism involved in this process. METHODS: Eighteen SD rats were randomly divided into 3 groups ( n= 6): normal control group (NC), diabetes mellitus group (DM) and LBP-treatment group (DM+LBP). The diabetic rat model was induced by single intraperitoneal injection of streptozotocin (STZ). The rats in DM+LBP group were treated with LBP at the dose of 1 mg/kg by gavage, once a day for 12 weeks. After the treatment, the weight and blood glucose, the generation of reactive oxygen species (ROS), the surviving retinal ganglion cells (RGCs) and amacrine cells and the protein expressions of nuclear factor E2-related factor 2 (Nrf2) and the heme oxygenase-1 (HO-1) were detected. RESULTS: The successful rate of diabetic model was 100%. Compared with NC group, the rats of DM group caused weight loss, elevated blood glucose, a marked increase of ROS generation and a significant decrease in the number of RGCs and amacrine cells (P＜0.01), and these effects were diminished or abolished by LBP treatment. Meanwhile, LBP significantly increased the expressions of Nrf2 and HO-1 in the retinas of diabetic rats (P＜0.01). CONCLUSION LBP can improve retinal oxidative stress and exert beneficial neuroprotective effects in diabetic rats, and its mechanism may be associated with the activation of the Nrf2/HO-1 antioxidant pathway.
Animals ; Diabetes Mellitus, Experimental ; Drugs, Chinese Herbal ; pharmacology ; Heme Oxygenase (Decyclizing) ; drug effects ; NF-E2-Related Factor 2 ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Retina ; drug effects

Objective To validate a cell infection-based quantitative RT-PCR for evaluating the potency of rotavirus vaccine. Methods According to the ICH ( the International Council for Harmonization) Harmonised Tripartite Guideline, the method was validated for its specificity, accuracy, precision, linearity and robustness. Results The method had good specificity as it could only amplify and detect the corre-sponding type of rotavirus strain. The recovery rates for determining the potency against rotaviruses of G2, G3 and G4 types were 97％ to 108％. The percent coefficient of variation ( CV) of both intra-plate and in-ter-plate precision was≤2. 62％, while the intraday and interday CV was≤1. 76％ and≤2. 27％, respec-tively. The CV between the two experimenters was≤7. 68％. The linearity range of the method was 4. 4-6. 5 UI for G2 type rotavirus, 3. 9-8. 3 UI for G3 type and 3. 5-8. 1 UI for G4 type. Good robustness was observed using the cells of 140 to 160 generations. Conclusions The cell infection-based quantitative RT-PCR was shown to have satisfactory specificity, accuracy, precision, linearity and robustness, suggesting that it was a suitable method for evaluating the potency of multivalent rotavirus live vaccines.