ObjectiveTo analyze the distribution of traditional Chinese medicine （TCM） syndrome elements in patients with immune-related adverse events （irAEs） associated with malignant tumor immunotherapy and to explore the influencing factors for the occurrence of irAEs. MethodsClinical data were retrospectively collected from malignant tumor patients treated with programmed death-1 （PD-1） inhibitors， including demographic information， tumor history， duration of immunotherapy， occurrence of irAEs， types and grades of irAEs （G1-G5）， and TCM four-diagnostic information. Patients were divided into irAEs group and the non-irAEs group based on the occurrence of irAEs. Propensity score matching （PSM） at a 1∶2 ratio was performed to balance baseline characteristics between groups. Syndrome elements before treatment and cumulative contributions of syndrome elements before and after irAEs onset were evaluated using the "Syndrome Elements Differentiation Scale". Logistic regression analysis was conducted to identify factors associated with the occurrence of irAEs. The use of glucocorticoids in the irAEs group was also analyzed. ResultsAfter 1∶2 matching， 59 patients were included in the irAEs group and 118 were in the non-irAEs group. No statistically significant differences were found between groups in terms of age， gender， primary tumor site， pathological type， or tumor stage （P＞0.05）. Patients in the non-irAEs group were more likely to have received targeted therapy， while the irAEs group had a longer duration of immunotherapy and a higher rate of positive programmed death-ligand 1 （PD-L1） expression （P＜0.05）. In total， 72 irAEs events occurred among 59 patients， with an overall incidence rate of 19.4% （59/304） and a grade 3~5 incidence rate of 6.8% （4/59）， mainly presenting as cardiotoxicity， nephrotoxicity， and pneumotoxicity.Before immunotherapy， the top three syndrome elements in the irAEs group were spleen （71.2%， 42/59）， kidney （42.4%， 25/59）， and lung （39.0%， 23/59）. For the pathogenic nature elements， yin deficiency （52.5%， 31/59）， phlegm （40.7%， 24/59）， and dampness （35.6%， 21/59） ranked highest. Compared to the non-irAEs group， the distribution of spleen， kidney， liver， yin deficiency， and qi deficiency elements showed significant differences in the irAEs group （P＜0.05）. After the occurrence of irAEs， the cumulative contributions of spleen， lung， stomach， heart， yin deficiency， qi deficiency， and yang hyperactivity elements increased significantly （P＜0.05）. Multivariate Logistic regression analysis indicated that duration of immunotherapy， spleen syndrome element， kidney syndrome element， liver syndrome element， yin deficiency element， and qi deficiency element were independent risk factors for irAEs （P＜0.05 or P＜0.01）. Among the irAEs patients， 15 received glucocorticoid combined with TCM treatment， while 6 received glucocorticoid therapy alone. Patients receiving combined treatment required lower doses and shorter courses of glucocorticoids compared to those treated with glucocorticoids alone （P＜0.05）. ConclusionIn malignant tumor patients， spleen， kidney， lung， yin deficiency， phlegm， dampness， and qi deficiency are the predominant syndrome elements before and after the occurrence of irAEs. However， elements such as heat and qi stagnation significantly increase after irAEs onset. Duration of immunotherapy， spleen， kidney， liver syndrome elements， yin deficiency， and qi deficiency are independent risk factors for the development of irAEs.

AIM:Study on the bioequivalence of rivaroxaban tablets from two different manufactur-ers in healthy subjects under fasting and postpran-dial conditions.METHODS:Adopting a single cen-ter,randomized,open,fasting and postprandial,four cycle,fully repeated crossover trial design.28 healthy male and female subjects were given oral administration of either the test or reference for-mulation(10 mg)on an empty stomach or in a post-prandial state,with a cleaning period of 7 days be-tween cycles.The concentration of rivaroxaban in the plasma(heparin sodium)of the subjects was measured using liquid chromatography tandem mass spectrometry(LC-MS/MS),and pharmacoki-netic(PK)parameters were calculated using Phoe-nix WinNonlin 7.0 software to evaluate the bio-equivalence of the test and reference formulations.RESULTS:Fasting group:After oral administration of the investigational drug,the Cmax of the test formula-tion and reference formulation were(200.96±68.99)ng/mL and(196.96±50.97)ng/mL,respec-tively,and the AUC0-t were(1 439.93±493.94)h·ng·mL-1 and(1 395.90±411.49)h·ng·mL-1,respectively,the AUC0-∞ were(1 506.56±511.47)h·ng·mL-1 and(1 451.94±417.89)h·ng·mL-1,respectively,the 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ were 91.87％-103.37％,95.00％-105.07％,95.33％-105.57％,respectively,the 90％CI of the intra-individual standard devia-tion ratio(SWT/SWR)for Cmax,AUC0-t,AUC0-∞were 0.88-1.73,0.74-1.45 and 0.72-1.41,respectively.Post-prandial group:After oral administration of the ex-perimental drug,the Cmax of the test and reference formulations were(241.23±54.44)ng/mL and(226.54±48.04)ng/mL,respectively,and the AUC0-t were(1 383.26±437.05)h·ng·mL-1 and(1 333.54±372.53)h·ng·mL-1,respectively,the AUC0-∞ were(1 404.01±439.89)h·ng·mL-1 and(1 352.31±374.45)h·ng·mL-1,respectively,the 90％confi-dence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ were 100.92％-110.50％,98.30％-108.31％,and 98.46％-108.39％,respective-ly,the 90％CI of the intra-individual standard devia-tion ratio(SWT/SWR)for Cmax,AUC0-t and AUC0-∞ were 0.63-1.29,0.78-1.61 and 0.79-1.61,respectively.CONCLUSION:Bioequivalence of the two prepara-tions in fasting and postprandial state in healthy subjects.

Objective:To investigate the surgical effect of total parathyroidectomy combined with calf subcutaneous autotransplantation in the treatment of secondary hyperparathyroidism.Method:From Dec 2018 to Dec 2022,31 patients with secondary hyperparathyroidism who underwent total parathyroidectomy combined with calf subcutaneous autotransplantation in our hospital were selected to analyze the therapeutic effect.Results:All 31 operations were successfully completed.A total of 120 parathyroid glands were removed,including 27 cases(87.10%)with 4 parathyroid glands and 4 cases(12.90%)with 3 parathyroid glands.The average length of hospitalization was(15.82±8.74)days.Compared with preoperative parathyroid hormone,the value of parathyroid hormone decreased by more than 50%after 20 min of total parathyroidectomy.The levels of serum calcium,phosphorus,iPTH and calcium-phosphorus product at each time point after operation were significantly lower than those before operation(P＜0.01).The symptoms of joint pain was significantly improved in all patients after operation.During the postoperative follow-up of 31 patients,1 patient was confirmed to have graft recurrence at 6 months after operation,which was surgically removed.Conclusion:Total parathyroidectomy combined with calf subcutaneous autotransplantation can effectively treat secondary hyperparathyroidism and significantly improve the quality of life.

BACKGROUND:Research has shown that vanillic acid has anti-inflammatory and anti-oxidative stress effects,but it is unclear whether it has a protective effect on endplate chondrocytes.OBJECTIVE:To explore the effect and mechanism of vanillic acid on endplate chondrocytes under inflammatory microenvironment.METHODS:(1)Primary endplate chondrocytes were isolated from the intervertebral disc of SD rats and identified by toluidine blue staining and collagenⅡ immunofluorescence.(2)The CCK-8 assay was employed to detect the effects of interleukin-1β and vanillic acid on the proliferation activity of endplate chondrocytes,in order to determine the concentration of vanillic acid for subsequent cell treatment.(3)An inflammatory microenvironment was simulated by adding 10 ng/mL interleukin-1β to the culture medium,and the endplate chondrocytes were treated with low,medium,and high mass concentrations of vanillic acid.The expression levels of inflammatory markers and extracellular matrix proteins were detected by western blot assay and immunofluorescence.(4)The expression of nuclear factor κB signaling pathway-related proteins was detected by western blot assay.RESULTS AND CONCLUSION:(1)The morphology of endplate chondrocytes in adherent culture was pike or triangular in shape,positive for toluidine blue staining and immunofluorescence for collagen Ⅱ,indicating that the experimentally extracted cells were endplate chondrocytes.(2)The CCK-8 assay results showed that treatment with 2.5,5,10,and 20 μg/mL vanillic acid for 24 hours did not significantly inhibit the proliferation of endplate chondrocytes.Compared with the interleukin-1β group,the viability of endplate chondrocytes treated with 5,10,and 20 μg/mL vanillic acid for 24 hours was significantly increased(P＜0.05).Therefore,5,10,and 20 μg/mL vanillic acid was selected as the low,medium,and high dose groups for subsequent treatment of endplate chondrocytes.(3)Compared with the model group(complete medium containing 10 ng/mL interleukin-1β),the expression of NOD-like receptor thermal domain associated protein 3(NLRP3),matrix metalloproteinase 13,matrix metalloproteinase 3,and tumor necrosis factor alpha protein in the endplate chondrocytes of the low,medium,and high doses of vanillic acid groups were significantly reduced(P＜0.05).(4)Compared with the model group,the protein expression of aggrecan and collagen Ⅱ in the endplate chondrocytes of the low,medium,and high dose groups of vanillic acid significantly increased(P＜0.05).(5)Compared with the model group,the protein expression of phospho-nuclear factor κB and phospho-inhibitor of nuclear factor κB in the endplate chondrocytes of the low,medium,and high dose groups of vanillic acid was significantly reduced(P＜0.05).(6)The above results indicate that vanillic acid may alleviate the inflammatory response and extracellular matrix degradation induced by interleukin-1β in rat endplate chondrocytes by inhibiting the activation of the nuclear factor κB signaling pathway.

Objective:To analyse the 3D-Flair MRI manifestations of the inner ear, vestibular function status, and their correlation with hearing treatment outcomes in patients with severe sudden sensorineural hearing loss (SSNHL), and to explore potential prognostic indicators for sudden deafness.Methods:The clinical data of adult patients with unilateral profound sudden sensorineural hearing loss were retrospectively analyzed in Otorhinolaryngology Department of Shandong Provincial ENT Hospital from March 2018 to August 2020. Patients were categorized based on the results of their inner ear 3D-Flair MRI into two groups: the normal MRI group and the abnormal MRI group. The abnormal group was further divided into three subgroups: those with non-absorbed high signal in the inner ear, those with absorbed high signal, and those with destruction of the blood-labyrinth barrier. SPSS 26.0 statistical software was applied to analyze the differences in hearing efficacy, caloric tests, vestibular evoked myogenic potentials (VEMP), video head impulse tests (vHIT), and the incidence of dizziness/vertigo among various patient groups.Results:A total of 191 patients with complete data were collected (97 males and 94 females, aged from 13 to 69 years old). There were 50 cases in the normal inner ear 3D-Flair MRI group. A total of 141 cases were found in the group with abnormal 3D-Flair MRI, including 50 cases of high signal unabsorbed, 71 cases of absorption high signal and 20 cases of blood labyrinth barrier destruction. There were no significant differences in age, sex, lateral ratio of hearing loss and course of disease among four groups (all P>0.05).The significant efficiencies of hearing recovery, in the group with normal 3D-FLAIR MRI were better than those in the abnormal group ( P<0.05) after treatment. Among the four groups, there were significant differences in the apparent efficiency and total effective rate between the normal group and the inner ear high signal absorption group ( χ2=4.007, P=0.045; χ2=6.925, P=0.009). The abnormal rates of bithermal caloric test, vHIT results and dizziness/vertigo symptoms in the abnormal group were higher than those in the normal group ( P<0.05). There were significant differences in oVEMP abnormality rate, vHIT abnormality rate and incidence of dizziness/vertigo among the three groups with 3D-FLAIR MRI abnormality ( P<0.05). There were significant differences in caloric test, oVEMP, vHIT abnormality rate and incidence of dizziness/vertigo among the four groups ( P<0.05). The positive rates of caloric test, cVEMP test and vHIT test in patients with dizziness/vertigo were higher than those in patients without dizziness/vertigo ( P<0.05). The abnormal rates of posterior semicircular canal and horizontal semicircular canal in patients with dizziness/vertigo were significantly increased ( P<0.05) than patients without dizziness/vertigo. The recovery rate, effective rate and total effective rate of patients without dizziness/vertigo were significantly better than those with dizziness/vertigo ( P<0.05). Conclusions:The 3D-Flair MRI of the inner ear and vestibular function tests have reference value for the prognosis assessment of patients with severe sudden sensorineural hearing loss. Abnormal 3D-FLAIR MRI of the inner ear, especially absorption high signal, is associated with high incidence of vestibular dysfunction and dizziness/vertigo, with poor prognosis. Patients with severe sudden sensorineural hearing loss who have symptoms of dizziness/vertigo are more likely to exhibit abnormal results in vestibular function tests, with a higher susceptibility to involvement of the posterior and horizontal semicircular canals.

Objective To evaluate the evidence about impact of physical activity(PA)on glycemic control and related health out-comes in patients with type 2 diabetes mellitus(T2DM).Methods Adhering to PRISMA guideline,systematic reviews and meta-analyses published between 2017 and 2024 were retrieved from the databases such as Medline,Embase and Cochrane Library.Two researchers independently ex-tracted data and assessed the quality using AMSTAR2.The included systematic reviews were systematically re-viewed.Results Eight systematic reviews were included,with six rated as high quality and two as low quality.Various forms of PA interventions,such as aerobic exercise,resistance training,combined training and high-intensity interval train-ing,might significantly reduce glycated hemoglobin,enhance cardiorespiratory fitness,lower cardiovascular risk factors(such as body mass,blood pressure and blood lipids),and decrease the risk of diabetes-related complica-tions and mortality in T2DM patients.Combined training and high-intensity training seemed to be better.Profes-sionally supervised PA was more effective.Conclusions Regular and multimodal PA is effective on glycemic control,and cardiovascular and metabolic risk factors in T2DM patients.It is advocated an individualized,diversified,adequately dosed(encouraging higher total dos-es),intensity-appropriate(promoting higher intensity),combined-mode and supervision-integrated PA strategies.

ObjectiveTo investigate the association between the maintenance treatment of modified Yiqi Huoxue Jiedu Formula （益气活血解毒方） or poly ADP ribose polymerase （PARP） inhibitors and the recurrence and metastasis of advanced ovarian cancer. MethodsA case-control study design was employed， dividing patients with advanced ovarian cancer into two groups based on the occurrence of recurrence and metastasis following first-line maintenance treatment. Patients with recurrence and metastasis comprised the case group， while those without recurrence and metastasis served as the control group. The previous first-line maintenance treatment method was set as the exposure factor in the study （with the use of modified Yiqi Huoxue Jiedu Formula defined as exposed and PARP inhibitors defined as unexposed）. Basic information was collected for both groups， including the achievement of satisfactory R0 surgery， age， stage， neoadjuvant chemotherapy， lymph node metastasis， germline BRCA1/2 mutations， homologous recombination deficiency positivity， first-line maintenance treatment method （modified Yiqi Huoxue Jiedu Formula or PARP inhibitors）， and CA125 levels after the last chemotherapy. The baseline data of the two groups were assessed for differences. If there exists difference， a 1∶1 nearest neighbor matching method was used for propensity score matching. Univariate and multivariate logistic regression analyses were employed to evaluate the association between the modified Yiqi Huoxue Jiedu Formula or PARP inhibitors and the recurrence and metastasis of ovarian cancer. ResultsA total of 201 patients with advanced ovarian cancer were included， with 97 in the case group and 104 in the control group. Both groups showed statistically significant differences in R0 surgery， stage， neoadjuvant chemotherapy， and CA125 levels after the last chemotherapy （P＜0.05）， indicating baseline imbalance. After propensity score matching， there were 71 patients in both the case and control groups， achieving baseline balance （P＞0.05）. Univariate logistic regression analysis indicated that the achievement of satisfactory R0 surgery （P = 0.006）， disease stage （P = 0.001）， the use of neoadjuvant chemotherapy （P = 0.024）， treatment modality （P = 0.006）， and CA125 levels after the last chemotherapy （P = 0.013） were associated with the recurrence and metastasis of ovarian cancer. Multivariate logistic regression analysis revealed that disease stage was an independent influencing factor for the recurrence and metastasis of ovarian cancer （P = 0.030）， whereas the P-value for the correlation between first-line maintenance treatment and ovarian cancer was 0.188. ConclusionFirst-line maintenance treatment of ovarian cancer patients with the use of modified Yiqi Huoxue Jiedu Formula or PARP inhibitors does not correlate with the recurrence and metastasis of ovarian cancer.

Objective To investigate the association of neuregulin 4(NRG4)and meteorin-like protein(Metrnl)with insulin resistance in patients with metabolic syndrome(MS).Methods From September to November 2023,totally 60 MS patients in Anhui No.2 Provincial People's Hospital were selected as MS group,and 60 physical examination healthy people were selected as control group.The changes of human mor-phological indicators,biochemical indicators,blood routine,NRG4,Metrnl,insulin resistance index(HOMA-IR)and other indicators in the two groups were observed,and the correlation between NRG4,Metrnl and HO-MA-IR and each index was analyzed,and the diagnostic value of NRG4 and Metrnl for MS was evaluated.Re-sults Compared with the control group,the levels of white blood cell count(WBC),alanine aminotransferase(ALT),uric acid(UA),triglyceride(TG),total cholesterol(TC),fasting insulin(FINS),HOMA-IR,body weight,body mass index(BMI),waist circumference,hip circumference,waist-hip ratio(WHR),and body fat ratio were significantly increased in MS group(P<0.05),however,high density lipoprotein cholesterol(HDL-C),NRG4,and Metrnl were significantly decreased(P<0.05).Spearman correlation analysis showed that serum NRG4 was positively correlated with Metrnl and HDL-C(P<0.05),and negatively correlated with TG,FINS,HOMA-IR,body weight,waist circumference,hip circumference,WHR,and ALT(P<0.05).Serum Metrnl was positively correlated with NRG4 and HDL-C(P<0.05),and negatively correlated with TG and hip circumference(P<0.05).Binary Logistic regression analysis showed that NRG4 and Metrnl were protective factors for MS(P<0.05).The receiver operating characteristic curve analysis showed that the sensitivity of NRG4,Metrnl,and their combination for diagnosing MS was 67%,41%,and 67%,respec-tively,the specificity was 71%,95%,and 86%,respectively,and the area under the curve was 0.713,0.635,and 0.787,respectively.Conclusion The levels of serum NRG4 and Metrnl are decreased in MS patients,and NRG4 is associated with insulin resistance.The combination of NRG4 and Metrnl has a certain diagnostic val-ue for MS.

Objective To investigate the relationship between the mean platelet volume(MPV)to platelet count(PLT)ratio(MPV/PLT),blood urea nitrogen(BUN)to lipoprotein a[Lp(a)]ratio[BUN/Lp(a)]and the prognosis of patients with acute exacerbation of chronic obstructive pulmonary disease(COPD).Methods A total of 106 patients with acute exacerbation of COPD admitted to the hospital from January 2021 to January 2024 were selected as the research objects.According to the prognosis,they were divided into sur-vival group(72 cases)and death group(34 cases).The results of routine laboratory tests,blood lipid and lipo-protein levels were compared between the two groups.Multivariate Logistic regression was used to analyze the influencing factors of death in patients with acute exacerbation of COPD.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of MPV/PLT and BUN/Lp(a)for the prognosis of pa-tients with acute exacerbation of COPD.Results Compared with the survival group,the invasive ventilation rate,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,C reactive protein(CRP),white blood cell count(WBC),MPV,BUN,MPV/PLT and BUN/Lp(a)were significantly increased in the death group(P＜0.05).The non-invasive ventilation rate,lymphocyte count,PLT and Lp(a)levels were signifi-cantly decreased(P＜0.05).Multivariate Logistic regression analysis showed that APACHE Ⅱ score,CRP,WBC,lymphocyte count,MPV,PLT,MPV/PLT,BUN,Lp(a)and BUN/Lp(a)were the influencing factors of death in patients with acute exacerbation of COPD(P＜0.05).ROC curve results showed that the sensitivity and specificity of MPV/PLT combined with BUN/Lp(a)for predicting the prognosis of patients with acute exacerbation of COPD were 88.2％and 84.7％,respectively,and the area under curve was 0.887.Conclusion MPV/PLT and BUN/Lp(a)are closely related to the prognosis of patients with acute exacerbation of COPD.The combination of MPV/PLT and BUN/Lp(a)has a high predictive value for the prognosis of patients.

Objective To investigate the levels of serum Vasostatin-1 and Autotaxin and their clinical sig-nificance in patients with pre-eclampsia(PE).Methods A total of 120 patients with PE(PE group)admitted to the hospital from January 2021 to January 2023 and 60 healthy pregnant women who underwent routine prenatal examinations during the same period(control group)were selected as the research subjects.Accord-ing to the severity of the disease,the patients in the PE group were divided into the severe PE group(65 ca-ses)and the mild PE group(55 cases).According to the pregnancy outcomes,they were divided into the poor group(57 cases)and the good group(63 cases).The levels of serum Vasostatin 1 and Autotaxin were detec-ted by enzyme-linked immunosorbent assay.Multivariate unconditional Logistic regression was used to analyze the influencing factors of adverse pregnancy outcomes of PE.The receiver operating characteristic curve was drawn to evaluate the predictive value of serum Vasostatin 1 and Autotaxin levels for adverse pregnancy out-comes of PE.Results Compared with the control group,the levels of serum Vasostatin 1 and Autotaxin in the PE group increased,and the differences were statistically significant(Z=-5.924,-6.188;both P＜0.001).Compared with the mild PE group,the levels of serum Vasostatin 1 and Autotaxin in the severe PE group in-creased,and the differences were statistically significant(Z=-4.667,-4.180;both P＜0.001).Compared with the good group,the levels of serum Vasostatin 1 and Autotaxin in the poor group increased with statisti-cal significance(Z=-5.500,-5.390;both P＜0.001).The results of Logistic regression analysis showed that severe PE(OR=3.383,95％CI:1.270-9.011),high 24 h urine protein(OR=1.888,95％CI:1.199-2.972),high Vasostatin-1(OR=1.022,95％CI:1.008-1.036)and Autotaxin(OR=4.370,95％CI:1.739-10.983)were independent risk factors for adverse pregnancy outcomes in patients with PE(P＜0.05).The area under the curve for the combined prediction of adverse pregnancy outcomes in PE patients by serum Va-sostatin 1 and Autotaxin levels was 0.864(95％CI:0.790-0.920),which was greater than predicted sepa-rately,which were 0.791(95％CI:0.708-0.860),0.786(95％CI:0.701-0.855),and the differences were statistically significant(Z=2.595,2.462;both P＜0.05).Conclusion Elevated serum Vasostatin-1 and Au-totaxin levels in PE patients are associated with the aggravation of the disease and adverse pregnancy out-comes.The combined detection of serum Vasostatin 1 and Autotaxin levels has a high predictive efficacy for the pregnancy outcomes of patients with PE.