Purpose::Vibrio vulnificus ( V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. Methods::An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. Results::In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival ( p = 0.014), reduced the serum creatinine ( p = 0.002), urea nitrogen ( p = 0.030), aspartate aminotransferase ( p = 0.029), and alanine aminotransferase ( p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid ( p = 0.225), liver ( p = 0.186), or kidney ( p = 0.637). Conclusion::Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Objective: To explore the possible mechanism of radiotherapy regulating the expression of PD-L1 in esophageal carcinoma. Methods: Three esophageal cancer cell lines (Eca109, Kyse150, TE1) were irradiated with different doses of X-rays, and 6 Gy+ AG490 group was set. The mRNA expression of PD-L1 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein expressions of PD-L1, STAT3, p-STAT3 were detected by western blotting and the protein level of IL-6 was detected by ELISA. Results: The mRNA expressions of PD-L1 in Eca109, Kyse150 and TE1 were 2.86±0.30, 960.01±21.27 and 106.78±6.67, higher than 1.07±0.15 in normal esophageal cell line HET-1A (P<0.01). The protein expressions of PD-L1 in Eca109, Kyse150 and TE1 were 0.091±0.036, 1.533±0.079 and 0.914±0.035, higher than 0.063±0.01 in normal esophageal cell line HET-1A (P<0.01). After 48 hours of 6 Gy irradiation, the protein expression levels of PD-L1 in Eca109, Kyse150 and TE1 were 0.135±0.007, 1.66±0.06 and 1.32±0.06, higher than 0.09±0.01, 1.21±0.05 and 0.93±0.03 of the 0 Gy group (P<0.01), while the protein expression levels of p-STAT3 in Eca109, Kyse150 and TE1 were 1.44±0.26, 0.75±0.04 and 1.92±0.17, higher than 0.18±0.05, 0.48±0.02 and 0.36±0.06 of the 0 Gy group (P<0.01). IL-6 protein expression increased significantly after different doses of irradiation (P<0.01). After the IL-6/STAT3 signaling pathway was blocked by the specific inhibitor AG490, the expressions of PD-L1 of Eca109, Kyse150 and TE1 in the 6 Gy+ AG490 groups were 0.11±0.03, 1.07±0.08 and 0.96±0.11, without significant differences of 0.09±0.01, 0.96±0.05 and 0.85±0.09 of the 0 Gy group (P>0.05), while the protein expressions of p-STAT3 were 0.76±0.11, 0.59±0.06 and 0.96±0.12, without significant differences of 0.67±0.08, 0.54±0.06 and 0.84±0.11 of the 0 Gy group (P>0.05). Conclusion: Radiotherapy may regulate the expression of PD-L1 in esophageal cancer cells through IL-6 / STAT3 signaling pathway.
B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Cell Proliferation ; Esophageal Neoplasms/radiotherapy* ; Humans ; Interleukin-6/metabolism* ; RNA, Messenger ; STAT3 Transcription Factor/metabolism* ; Signal Transduction

OBJECTIVE: To investigate the effects of Bax inhibitor 1 (BI- 1) and optic atrophy protein 1 (OPA1) on vascular calcification (VC). METHODS: Mouse models of VC were established in ApoE-deficient (ApoE^-/-) diabetic mice by high-fat diet feeding for 12 weeks followed by intraperitoneal injections with N^ε-carboxymethyl-lysine for 16 weeks. ApoE^-/- mice (control group), ApoE^-/- diabetic mice (VC group), ApoE^-/- diabetic mice with BI-1 overexpression (VC + BI-1^TG group), and ApoE^-/- diabetic mice with BI-1 overexpression and OPA1 knockout (VC+BI-1^TG+OPA1^-/- group) were obtained for examination of the degree of aortic calcification using von Kossa staining. The changes in calcium content in the aorta were analyzed using ELISA. The expressions of Runt-related transcription factor 2 (RUNX2) and bone morphogenetic protein 2 (BMP-2) were detected using immunohistochemistry, and the expression of cleaved caspase-3 was determined using Western blotting. Cultured mouse aortic smooth muscle cells were treated with 10 mmol/L β-glycerophosphate for 14 days to induce calcification, and the changes in BI-1 and OPA1 protein expressions were examined using Western blotting and cell apoptosis was detected using TUNEL staining. RESULTS: ApoE^-/- mice with VC showed significantly decreased expressions of BI-1 and OPA1 proteins in the aorta (P=0.0044) with obviously increased calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 (P= 0.0041). Overexpression of BI-1 significantly promoted OPA1 protein expression and reduced calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 (P=0.0006). OPA1 knockdown significantly increased calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 in the aorta (P=0.0007). CONCLUSION BI-1 inhibits VC possibly by promoting the expression of OPA1, reducing calcium deposition and inhibiting osteogenic differentiation and apoptosis of the vascular smooth muscle cells.
Animals ; Apolipoproteins E/metabolism* ; Calcium/metabolism* ; Caspase 3/metabolism* ; Cells, Cultured ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Diabetes Mellitus, Experimental/pathology* ; GTP Phosphohydrolases/metabolism* ; Membrane Proteins/metabolism* ; Mice ; Mice, Knockout ; Muscle, Smooth, Vascular/pathology* ; Myocytes, Smooth Muscle/pathology* ; Optic Atrophy, Autosomal Dominant/pathology* ; Osteogenesis ; Vascular Calcification/pathology* ; bcl-2-Associated X Protein/metabolism*

Objective: To investigate hypertriglyceridemia and hepatomegaly caused by Schisandrae Sphenantherae Fructus (FSS) and Schisandra chinensis Fructus (FSC) oils in mice. Methods: Mice were orally administered a single dose of Schisandrae Fructus oils. Serum and hepatic triglyceride (TG), triglyceride transfer protein (TTP), apolipoprotein B48 (Apo B48), very-low-density lipoprotein (VLDL), hepatocyte growth factor (HGF), alanine aminotransfease (ALT) and liver index were measured at 6-120 h post-dosing. Results: FSS and FSC oil caused time and dose-dependent increases in serum and hepatic TG levels, with maximum increases in the liver (by 297% and 340%) at 12 h post-dosing and serum (244% and 439%) at 24-h post-dosing, respectively. Schisandrae Fructus oil treatments also elevated the levels of serum TTP by 51% and 63%, Apo B48 by 152% and 425%, and VLDL by 67% and 38% in mice, respectively. FSS and FSC oil treatments also increased liver mass by 53% and 55% and HGF by 106% and 174%, but lowered serum ALT activity by 38% and 22%, respectively. Fenofibrate pre/ co-treatment attenuated the FSS and FSC oil-induced elevation in serum TG levels by 41% and 49% at 48 h post-dosing, respectively, but increased hepatic TG contents (by 38% and 33%, respectively) at 12 h post-dosing. Conclusions: Our findings provide evidence to support the establishment of a novel mouse model of hypertriglyceridemia by oral administration of FSS oil (mainly increasing endogenous TG) and FSC oil (mainly elevating exogenous TG).

ObjectiveTo establish the determination for index components in benchmark samples of Erdongtang， and clarify the content and transfer rate rages of index components in 15 batches of benchmark samples， and to explore the quantity transfer of index components of decoction pieces to benchmark samples. MethodFifteen batches of benchmark samples were prepared， the contents of mangiferin， baicalin and glycyrrhizic acid were determined by high performance liquid chromatography （HPLC）-diode array detector （DAD）， the mobile phase was acetonitrile （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-10 min， 10%-17%A； 10-25 min， 17%-19%A； 25-28 min， 19%-25%A； 28-45 min， 25%-33%A； 45-46 min， 33%-45%A； 46-60 min， 45%-55%A）， detection wavelength was set at 254 nm. Contents of timosaponin BⅡ and the sum of protoneodioscin and protodioscin were determined by HPLC-evaporative light scattering detector （ELSD）， the mobile phase was acetonitrile （A）-water （B） for gradient elution （0-20 min， 24%A； 20-25 min， 24%-27%A； 25-33 min， 27%-28%A； 33-36 min， 28%-90%A； 36-41 min， 90%-24%A）. ResultThe methodological verification of the established method was good， which could be used for determination of five index components in benchmark samples. The content ranges of mangiferin， baicalin， glycyrrhizic acid， timosaponin BⅡ， and the sum of protoneodioscin and protodioscin in 15 batches of benchmark samples of Erdongtang were 0.14%-0.23%， 2.40%-3.37%， 0.07%-0.44%， 0.43%-0.95%， and 0.15%-0.47%， the transfer rate ranges of them were 33.90%-52.15%， 84.46%-105.61%， 22.59%-93.86%， 38.07%-61.43%， and 53.28%-96.11%， respectively. ConclusionThe consistencies of transfer rate of mangiferin， baicalin， timosaponin BⅡ and the sum of protoneodioscin and protodioscin （except glycyrrhizic acid） between decoction pieces and benchmark samples of Erdongtang are good， indicates that the transfer rates of 4 index components are stable during the preparation process of benchmark samples， which can provide data support for research and development of the compound preparation of this formula.

Objective: To investigate the possible pathophysiological mechanism of laryngopharyngeal reflux (LPR) in the development of lingual tonsil hypertrophy (LTH). Methods: The lingual tonsil tissues were collected from 73 patients [48 males and 25 females, aged from 24 to 76 (52.86±12.04) years] who underwent surgery for laryngopharyngeal diseases at the Department of Otolaryngology and Head and Neck Surgery, Southern Hospital of Southern Medical University from October 2019 to December 2020, and the lingual tonsil grade (LTG), reflux symptom index (RSI) and reflux finding score (RFS) were assessed. The expression of pepsin in LTH was detected by immunohistochemistry. The coexpression of pepsin and macrophages were detected by immunohistofluorescence. In vitro, cytological experiments and pathway assays were performed on macrophages stimulated by pepsin. Pathway alterations of macrophages in pepsin-positive high-grade LTH were detected by double-fluorescence immunohistochemistry. Data were analyzed by SPSS 20.0 software. Results: There were 44 clinically significant LPRD patients with LTG 3 and 4, and the pepsin positive rate was 88.6% (39/44). While, the pepsin positive rate of LTG 1 and 2 was 48.3% (14/29). LTG was significantly positively correlated with RFS/RSI positive rate(χ²=23.01/19.62, P<0.001/0.001; r=0.54/0.51, P<0.001/0.001) and pepsin tissue staining intensity (H=21.58, P<0.001; r=0.53, P<0.001), respectively. Pepsin and macrophages were clearly colocalized in high grade LTH. In vitro, pepsin promoted macrophage proliferation (P<0.05) and production of IL-6/IL-8 (P<0.05). Pepsin significantly up-regulated the p38/JNK MAPK pathway in macrophages (P<0.05). Pepsin up-regulated the expression of IL-6 and IL-8 of macrophages by activating the p38 MAPK pathway (P<0.05), and up-regulated the expression of IL-8 by activating the JNK pathway (P<0.05). The p38/JNK MAPK pathways were highly expressed in macrophages of pepsin-positive LTH (P<0.05). Conclusions: LPR is an important pathogenic factor in LTH. Macrophages may mediate pepsin-induced inflammation and the pathogenesis of LTH.
Female ; Male ; Humans ; Palatine Tonsil ; Pepsin A ; Interleukin-6 ; Interleukin-8 ; Hypertrophy ; Macrophages ; Laryngopharyngeal Reflux

Lateral epicondylitis is a common clinical disease with characteristics of lateral elbow pain, insidious onset and easy recurrence, which can cause forearm pain and decreased wrist strength, seriously affecting patients′ daily life and work. Although there are various treatment methods for lateral epicondylitis with different effects, standard treatments are still lacking nowadays. Platelet-rich plasma (PRP) has good effects on bone and tendon repair, and is now widely used in the treatment of lateral epicondylitis. However, there is a lack of a unified understanding of the technology and specifications of PRP in the treatment of lateral epicondylitis. Therefore, the Sports Medicine Branch of the Chinese Medical Association and Physical Medicine and Rehabilitation Branch of the Chinese Medical Association organized experts in the fields of sports medicine and rehabilitation medicine in China to formulate the "clinical expert consensus on platelet-rich plasma treatment for lateral epicondylitis (2022 version)", and proposed suggestions based on evidence-based medicine mainly from the concept, epidemiology and pathophysiology of lateral epicondylitis, symptoms, signs and imaging manifestations of lateral epicondylitis, PRP concept and application component requirements, quality control of PRP preparation technology, indications and contraindications of PRP in the treatment of lateral epicondylitis, PRP injection in the treatment of lateral epicondylitis, application of PRP in the operation of lateral epicondylitis, related problems after PRP treatment of lateral epicondylitis, evaluation of the results after PRP treatment of lateral epicondylitis, and health and economic evaluation of PRP treatment of lateral epicondylitis, so as to provide guidance for clinical diagnosis and treatment.

Objective To investigate the current status of nutritional knowledge and skills of fast-food takeout practitioners in Chengdu City,so as to provide evidence for nutritional literacy education among takeout practitioners.Methods A questionnaire survey was conducted among 832 employees of fast-food takeout restaurants in Chengdu from April to September in 2019 through a multi-stage random sampling strategy.Results The awareness rate of nutritional knowledge of fast-food takeout practitioners in Chengdu was 77.28%,and the correct rates of answers to daily oil intake for adults,daily drinking water for adults and daily salt intake for adults in the Dietary Guidelines for Chinese Residents were respectively 17.43%,22.60% and 25.36%.In addition,the proportion of practitioners with the ability to estimate the recommended intake of food for a meal,the ability to estimate condiments intake and the ability to interpret nutrition labels were 8.77%,8.77% and 15.02%,respectively.The awareness rate of nutritional knowledge was the lowest(71.47%)in the practitioners aged≤25 and the highest(84.53%)in those aged 26-39,and the difference was statistically significant(χ
Adult ; Feeding Behavior ; Humans ; Nutritional Status ; Restaurants ; Surveys and Questionnaires