OBJECTIVE To screen potential adverse drug event （ADE） signals for the treatment of multiple sclerosis （MS） with ofatumumab， and to provide reference for the safe use of drugs in clinical practice. METHODS Using “ofatumumab” and the trade name “Kesimpta” as the search keywords， adverse event （AE） reports related to ofatumumab included in FDA Adverse Event Reporting System database from January 2009 to December 2023 were screened， and their reason contained the “multiple sclerosis”； ADE signal mining and analysis were conducted by reporting odds ratio method and proportional reporting ratio method. RESULTS A total of 21 759 eligible AE reports were selected， involving 62 449 AE cases； 27 system organ classes included general diseases and various reactions at the site of administration （15 021 cases）， neurological diseases （9 668 cases）， infectious and invasive diseases （5 967 cases）， injury， poisoning and surgical complications （4 952 cases）， musculoskeletal and connective tissue disorders （4 647 cases）. A total of 21 759 AE reports correspond to 606 ADE signals， including 234 ADE positive signals. A total of 107 ADE positive signals were not included in drug instruction of ofatumumab， including flu-like diseases， nasopharyngitis， cough， urinary tract infection， sore throat， insomnia， runny nose， anemia， hair loss， atrial fibrillation， and thrombocytopenia， etc. CONCLUSIONS In the process of using ofatumumab for MS， sufficient attention should be paid to ADE included in drug instructions. The ADE with strong signal strength screened in this study should also be paid special attention to， such as flu-like diseases， hemocytopenia， temperature intolerance， optic neuritis， and moyamoya disease. The increased risk of infection， cardiovascular disease， and potential damage to the respiratory and spiritual systems caused by ofatumumab can not be ignored.

OBJECTIVE To establish the UHPLC fingerprint of Miao Medicine Ficus tikoua Bur., study its spectrum-effect relationship with antioxidant activity, and screen the antioxidant active components. METHODS UHPLC was used to establish the fingerprint of Ficus tikoua Bur.. Evaluation System for Similarity of Chromatographic Fingerprint of Chinese Herbal Medicine (Version 2012) was used to evaluate the similarity and identify the common peaks. SPSS 16.0 and SIMCA 14.1 software were used for hierarchical cluster analysis(HCA) and principal component analysis(PCA). The 1,1-diphenyl-2-picrylhydrazyl(DPPH) free radical scavenging method, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt(ABTS) free radical scavenging method and total antioxidant capacity method were used to evaluate the antioxidant activity of 16 batches of ethanol extracts from Ficus tikoua Bur. Three methods including grey relational analysis(GRA), bivariate correlation analysis and partial least squares regression(PLSR) were used to study the spectrum-effect relationship. RESULTS The UHPLC fingerprints of 16 batches of Ficus tikoua Bur. were established and 13 common peaks were identified. The similarities were 0.613−0.996. At the same time, it was identified that peak 9 was rutin, peak 10 was isoquercetin, and peak 12 was narcissin. The results of HCA showed that the samples were clustered into two categories, which was consistent with the PCA results. Sixteen batches of Ficus tikoua Bur. had different degrees of antioxidant activity. The results of GRA showed that the correlation between 13 common peaks and antioxidant activity was >0.8, and all of them had high correlation. The results of bivariate correlation analysis and PLSR analysis showed that the correlation coefficient and regression coefficient of peak 5, peak 9(rutin), peak 10(isoquercetin), peak 11 and peak 12(narcissin) were positively correlated with antioxidant activity, and the contribution rate was larger(variable importance in projection>1), which were the main active components of antioxidant activity. CONCLUSION All the 16 batches of Ficus tikoua Bur. have good antioxidant activity, and its antioxidant effect is the result of the synergistic action of the internal antioxidant component group. The components corresponding to the common peaks 5, 9, 10, 11, 12 are closely related to their antioxidant activity, revealing the pharmacodynamic material basis of the antioxidant activity of Ficus tikoua Bur.

Objective:To analyze long-term prognosis and influencing factors of recurrence in vocal fold leukoplakia treated by endoscopic cordectomy with CO 2 laser. Methods:A retrospective review was conducted on 599 patients with vocal fold leukoplakia [566 males and 33 females, aged 17-84 years (median age 55 years)], undergoing endoscopic cordectomy by CO 2 laser under general anesthesia at the Department of Otorhinolaryngology Head and Neck Surgery of Beijing Tongren Hospital, Capital Medical University, from January 2000 to December 2023. The study analyzed the clinical features, pathological grade, surgical methods, postoperative voice function, recurrence, malignant changes and analyzed the long-term efficacy and and its influencing factors. The patients were followed up for a duration of 6-249 months postoperatively, with a median follow-up time of 48 months. SPSS 20.0 software was used for statistical analysis. Results:Among the 599 patients, the histopathological grades included simple squamous cell hyperplasia in ( n=264, 44.08%), mild dysplasia ( n=96, 16.03%), moderate dysplasia ( n=74, 12.35%), severe dysplasia( n=43, 7.81%), carcinoma in situ( n=35, 5.84%), and carcinoma in situ with microinvasion( n=87, 14.52%). The 3-year and 5-year overall recurrence rates were 12.91% and 16.00%, respectively. In patients with precancerous lesion, 3.91% of recurrences presented with an upgraded pathologic grade and 2.34% evolved into carcinoma. The risk of recurrence was higher in lesions involving the anterior commissure, larger lesions, significant reduction/absence of mucosal waves, neovascularization/suspected neovascularization, and pathology of dysplasia/carcinoma in situ/carcinoma in situ with microinvasion( F=44.76,21.54,11.55,8.78,23.20,respectively, P<0.05). Additionally, patients with recurrent disease exhibited higher reflux symptom index scores compared to those without recurrence. Exophytic lesion characteristics and the inability to cease smoking postoperatively were identified as independent risk factors for recurrence with an upgraded pathological grade, with odds ratios of 8.675 and 11.380 times greater than those with non-exophytic lesions and successful smoking cessation, respectively. At the 6-months postoperative assessment, patients who underwent subepithelial cordectomy (typeⅠ) demonstrated a statistically significant increase in fundamental frequency ( t=-3.38, P<0.05), and while other voice acoustic parameters were not significantly different.Conversely, those who underwent transmuscular cordectomy (TypeⅢ) exhibited significant alterations in multiple voice acoustic parameters when compared to preoperative values ( P<0.05). Furthermore, postoperative vocal fold adhesions developed in 84 patients with 13 of these individuals requiring surgical intervention for adhesion release. Conclusions:Lesions involving the anterior commissure, larger lesions, pathology of dysplasia/carcinoma in situ/carcinoma in situ with microinfiltration, significant reduction/absence of vocal fold mucosal waves, and neovascularization visible under NBI are indicative of an increased risk of recurrence, whereas exophytic lesions and the inability to cease smoking postoperatively significantly increase the risk of recurrence with elevated pathologic grade. Recovery of postoperative voice quality is procedure-dependent, underscoring the importance of surgical approach selection in the management of vocal fold leukoplakia.

Objective:To assess the prevalence and type of tissue prolapse (TP) occurring after endovascular treatment (ET), investigate the association between TP types and plaque morphological characteristics before ET, and observe in-stent neointimal hyperplasia (NIH) using optical coherence tomography (OCT).Methods:Patients who underwent carotid artery stenting and received pre- and post-ET OCT assessment at Jinling Hospital between July 2018 and December 2019 were collected. Baseline plaque characteristics and TP features were evaluated using OCT. The TPs were classified into two categories: smooth TP (STP) and irregular and/or high attenuated TP (I/HTP). The association between I/HTP and plaque characteristics was analyzed, while NIH feature was also summarized.Results:A total of 29 patients were included in the study, of whom 23 patients (79.3%) presented with TP. Among these 23 patients, 9 were classified as I/HTP and 14 were classified as STP. Compared with STP, I/HTP was more commonly observed in lipid-rich plaques (7/9 vs 2/14, P=0.007), and lesions with cap rupture (7/9 vs 4/14, P=0.036). Additionally, the longitudinal length of TP appeared to be longer in cases with I/HTP compared to those with STP [3.0 (1.5, 4.6) mm vs 1.1 (0.7, 3.2) mm, Z=1.294, P=0.201]. Six patients underwent OCT follow-up for a mean duration of 6.7 months, of whom 3 patients with I/HTP showed severe heterogeneous NIH (50.1%-61.8%), while 1 patient with STP and 2 patients without TP only demonstrated mild NIH. Conclusions:The study observed that I/HTP was commonly found in plaques with larger lipid core and/or cap rupture, and suggested a potential relationship between I/HTP and NIH. These preliminary findings obtained from a limited sample should be verified by prospective large-scale studies.

OBJECTIVE To provide reference for quality control of Gentiana rhodantha. METHODS Taking 52 batches of G. rhodantha as subject， ultra-high performance liquid chromatography （UPLC） fingerprint was adopted. The similarity of 52 batches of medicinal materials samples was evaluated by the Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicine （2004A edition）； the content of mangiferin was determined； chemometric analyses [cluster analysis， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA）] were performed. RESULTS UPLC fingerprints of 52 batches of G. rhodantha were established， 17 common peaks were identified， and 6 of them were identified， which were loganic acid （peak 1）， neomangiferin （peak 3）， swertiamarin （peak 5）， dangyin （peak 6）， mangiferin （peak 7） and isoorientin （peak 9）. The similarities of 52 batches of medicinal materials samples were all greater than 0.9； cluster analysis showed that S1-S46， S48-S52 clustered into one class， and S47 alone； PCA results showed that the cumulative variance contribution rate of the first six principal components was 82.928%； OPLS-DA results showed that the corresponding components of swertiamarin， mangiferin and chemical composition represented by peak 4， 14， 15， 16 were the main iconic components affecting the quality differences of G. rhodantha medicinal materials. The contents of mangiferin in 52 batches of medicinal material samples ranged from 18.2 to 101.0 mg/g， mostly in accordance with 2020 edition of Chinese Pharmacopoeia. CONCLUSIONS The established UPLC fingerprint and chemometric analysis methods combined with content determination method of mangiferin can comprehensively evaluate the quality of G. rhodantha.

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.

Objective:To study the phenotype and genotype distribution of Yersinia pestis ( Y. pestis) in different natural foci of plague in China, so as to provide scientific basis for plague prevention and control. Methods:A total of 2 184 strains of Y. pestis isolated from different time periods, regions, hosts and vectors in 11 plague natural foci of China since 1943 were selected for biochemical type identification, glycolysis test, virulence factor test [capsule antigen (F1), pesticin Ⅰ (Pst Ⅰ), virulence antigen factor (VWa), pigmentation factor (Pgm)], different region (DFR) typing and clustered regularly interspaced short palindromic repeats (CRISPR) typing. Results:There were 16 biochemical types of Y. pestis in the natural foci of plague in China, and each biochemical type showed obvious regional distribution in each foci. Most strains were positive for ass hide glue glycolysis (89.79%, 1 961/2 184), maltose (80.13%, 1 750/2 184), glycerol (94.23%, 2 058/2 184), and denitrification (82.78%, 1 808/2 184), and negative for rhamnose (88.78%, 1 939/2 184) and melibiose (85.62%, 1 870/2 184). Virulence factor test results showed that 99.95% (2 183/2 184) of Y. pestis were F1 positive; 99.73% (2 178/2 184) of Y. pestis can produce Pst Ⅰ; 73.31% (1 601/2 184) of Y. pestis were VWa positive and 26.69% (583/2 184) were VWa negative; Pgm positive strains accounted for 72.62% (1 586/2 184), Pgm negative strains accounted for 21.52% (470/2 184), and Pgm mixed type strains accounted for 5.86% (128/2 184). According to DFR typing results, there were 52 genotypes in 2 184 strains of Y. pestis, of which 19 were major genotypes and 33 were minor genotypes. CRISPR typing revealed 16 major genotypes, of which 7 were newly discovered. Conclusion:The phenotypes and genotypes of Y. pestis in various natural foci of plague in China are diverse and have geographical distribution characteristics.

Objective To explore the effect of Yunnan specialty rice products on blood sugar by measuring the glycemic index of 5 Yunnan special rice foods:rice noodles,rice cakes,rice rolls,sour rice noodles and dry rice noodles.Methods Following the national standard method to determine the carbohydrate content of 5 Yunnan specialty rice products,and the target amount of the test substance was calculated.Food Glycemic Index Determination Method was used to determine the glycemic index of 5 Yunnan specialty rice products and observe their impact on blood sugar.Results The GI value of Yunnan specialty food rice noodle is 63,rice cake is 64,rice roll is 46,sour rice noodles is 38,and dry rice noodles is 33.Conclusion Yunnan specialty foods rice noodle and rice cake belong to medium GI foods,and diabetes patients should reduce consumption;rice roll,sour rice noodles,and dry rice noodles belong to low GI foods and can be a better staple food source for diabetes patients.

Objective:To explore the protective effect of methyl eugenol (Me) on islet ischemia/reperfusion (I/R) injury and elucidate its underlying mechanism.Methods:The islets were isolated and purified from 6-8 week male BALB/c mice and divided into four groups of normal control (normal culture without any treatment), hypoxia/reoxygenation (H/R treatment), H/R+ dimethyl sulfoxide (DMSO dosing plus H/R treatment) and H/R+ Me (Me dosing plus H/R). Viability of islet cells in each group was detected by acridine orange (AO)/propidium iodide (PI) double stain.Function of islet cells (insulin secretion) was measured by enzyme-linked immunosorbent assay (ELISA). Murine islet β Min6 cells were selected for detecting the effect of Me on the proliferative activity of normal cultured and H/R treated islet cells under different concentration gradients by CCK8.Then Min6 cells were divided into four groups of normal, H/R, H/R+ DMSO and H/R+ Me.The definition of group was the same as that of primary murine islets.Flow cytometry and Hoechst 33342 nuclear stain were utilized for detecting cell apoptotic rate in each group.The protein expressions of p-JNK, p-p38, JNK, p38, Bcl-2 and Bax were detected by Western blot.And the data were processed by one-way ANOVA or t test.Results:The proportion of dead islet cells in H/R group was (29.47±2.65)% and it was significantly lower than that in normal group (7.63±1.53)%.And the inter-group differences were statistically significant ( P<0.001). The proportion of dead islet cells was (20.63±3.07)% in H/R+ Me group.It was higher than that in H/R group (29.47±2.65)% and in H/R+ DMSO group (30.13±1.50)% and inter-group difference was statistically significant ( P<0.05 & P<0.01). Under the stimulation of high glucose, the insulin secretion level of islet in H/R+ Me group was (1.76+ 0.08) mg/L, which was higher than that in H/R group and H/R+ DMSD group(1.24±0.14)mg/L and(1.27±0.05)mg/L, and the difference was statistically significant[(1.76±0.08) vs. (1.24±0.14) mg/L; (1.76±0.08) vs.(1.27±0.05) mg/L, P<0.01]. There was no significant effect on cell viability after Me dosing within a certain concentration range (0-40 μmol/L). After Me dosing (5 μmol/L), cell viability of H/R-treated Min6 cells was significantly higher than that without Me.And the difference was statistically significant[(1.19±0.03) vs.(1.00±0), P<0.01]. As compared with H/R and H/R+ DMSO groups, overall apoptotic rate declined in H/R+ Me group (Hoechst 33342 stain: 14.50%±1.05% vs. 23.30%±1.18%, 14.50%±1.05% vs. 22.77%±1.75%, P<0.001; Flow cytometry: 4.36%±0.54% vs. 21.44%±1.02%, 4.36%±0.54% vs. 21.68%±3.06%, P<0.01). The expressions of p-JNK and p-p38 were down-regulated (p-JNK: 0.77±0.06 vs. 1.03±0.05, 0.77±0.06 vs.0.93±0.04, P<0.001; p-p38: 0.80±0.05 vs. 1.01±0.08; 0.80±0.05 vs. 1.00±0.05, P<0.05) while Bcl-2/Bax ratio rose (1.62±0.13 vs. 0.72±0.10, 1.62±0.13 vs. 0.74±0.13, P<0.01). Conclusions:Me can improve the viability and function of islets and suppress the apoptosis of Min6 cells after H/R.The mechanism is correlated with JNK and p38 MAPK signaling pathways.

ObjectiveTo investigate the effects of Huashi Runzao prescription （HRP） on the histopathological injury and function of submandibular gland in naive non-obese diabetic （NOD/Ltj） mouse model of Sjögren's syndrome （SS） and its regulatory effect on aquaporin 5 （AQP5） expression in submandibular gland cells. MethodThe SS model was induced in NOD/Ltj mice. The NOD/Ltj female mice aged nine weeks were selected and randomly assigned into model group，HRP group （7.15 g·kg^-1·d^-1），and hydroxychloroquine （HCQ） group （1.30 g·kg^-1·d^-1）， and female BALB/c mice in the same age were selected and assigned into the normal group， with six mice in each group. Drug intervention lasted eight weeks. The water consumption and salivary flow rate （SFR） of each group were recorded. The pathological staining results of the submandibular gland of mice in each group were observed and scored. AQP5 expression was determined by immunohistochemistry （IHC） and Western blot. ResultCompared with the normal group， the model group showed increased water consumption （P<0.05） and reduced SFR （P<0.05）. Compared with the model group， the HRP group showed decreased water consumption （P<0.05） and increased SFR （P<0.05）， and the HCQ group showed increased SFR （P<0.05）. In terms of histopathological results of the submandibular gland，compared with the normal group，the model group showed increased pathological score， number of lymphocyte infiltration foci，and percentage of lymphatic infiltration area （P<0.05）. Compared with the model group， the HRP group showed reduced pathological scores and number of lymphocyte infiltration foci （P<0.05）， and the HRP group and the HCQ group showed reduced percentage of lymphatic infiltration area（P<0.05）. The results of IHC and Western blot showed that compared with the normal group，the model group showed down-regulated expression level of AQP5 protein （P<0.05）， and compared with the model group and the HCQ group，the HRP group showed up-regulated expression level of AQP5 protein （P<0.05）. ConclusionHRP can improve the secretion function of submandibular gland acinous cells and glandular structure injury in SS model mice， and its mechanism may be related to the up-regulation of AQP5 protein expression level in submandibular gland cells.