OBJECTIVE: To explore the neuroprotective effects of Xuefu Zhuyu Decoction (XFZYD) based on in vivo and metabolomics experiments. METHODS: Traumatic brain injury (TBI) was induced via a controlled cortical impact (CCI) method. Thirty rats were randomly divided into 3 groups (10 for each): sham, CCI and XFZYD groups (9 g/kg). The administration was performed by intragastric administration for 3 days. Neurological functions tests, histology staining, coagulation and haemorheology assays, and Western blot were examined. Untargeted metabolomics was employed to identify metabolites. The key metabolite was validated by enzyme-linked immunosorbent assay and immunofluorescence. RESULTS: XFZYD significantly alleviated neurological dysfunction in CCI model rats (P<0.01) but had no impact on coagulation function. As evidenced by Evans blue and IgG staining, XFZYD effectively prevented blood-brain barrier (BBB) disruption (P<0.05, P<0.01). Moreover, XFZYD not only increased the expression of collagen IV, occludin and zona occludens 1 but also decreased matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2), which protected BBB integrity (all P<0.05). Nine potential metabolites were identified, and all of them were reversed by XFZYD. Adenosine was the most significantly altered metabolite related to BBB repair. XFZYD significantly reduced the level of equilibrative nucleoside transporter 2 (ENT2) and increased adenosine (P<0.01), which may improve BBB integrity. CONCLUSIONS XFZYD ameliorates BBB disruption after TBI by decreasing the levels of MMP-9 and COX-2. Through further exploration via metabolomics, we found that XFZYD may exert a protective effect on BBB by regulating adenosine metabolism via ENT2.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Adenosine/metabolism* ; Male ; Rats, Sprague-Dawley ; Rats

Objective:To evaluate the value of a combined model based on primary lesion 18F-fluorodeoxyglucose ( 18F-FDG) PET/CT radiomics for predicting lymph node metastasis in non-small cell lung cancer (NSCLC) . Methods:A retrospective analysis was conducted on the clinical data of 203 NSCLC patients who underwent pre-treatment PET/CT imaging at Nanjing Drum Tower Hospital from June 2013 to July 2023. Patients were randomly assigned to the training set ( n=142) and the validation set ( n=61) at a ratio of 7∶3. A predictive model was developed in the training set, and its predictive performance and clinical application value were assessed in both the training and validation sets. Traditional PET/CT parameters and PET/CT radiomics features of the primary lesion were obtained by 3D-slicer software. Least absolute shrinkage and selection operator (LASSO), random forest, and extreme gradient boosting were performed to extract features. Support vector machine was used to construct a radiomics score (Radscore). Univariate and multivariate logistic regression analysis was used to predict the influencing factors of lymph node metastasis in NSCLC patients and to establish models. Predictive performance of the models was evaluated by receiver operator characteristic (ROC) curves and clinical application value was assessed by calibration curves and decision curve analysis (DCA) . Results:Among 203 NSCLC patients, 116 had lymph node metastasis, with 64 cases in the training set and 52 cases in the validation set. Three complementary classical machine learning methods were used for feature screening, and finally 10 radiomics features were obtained. The optimal threshold for Radscore-PET was 0.43 and the optimal threshold for Radscore-CT was 0.39. Univariate analysis showed that, sex ( OR=0.48, 95% CI: 0.24-0.95, P=0.036), tumor marker levels ( OR=3.81, 95% CI: 1.84-7.91, P<0.001), long diameter of tumor ( OR=2.56, 95% CI: 1.27-5.16, P=0.009), short diameter of tumor ( OR=3.73, 95% CI: 1.75-7.92, P=0.001), vacuolar sign ( OR=0.32, 95% CI: 0.12-0.86, P=0.024), ring-like metabolism ( OR=3.67, 95% CI: 1.33-10.13, P=0.012), maximum standardized uptake value (SUV max) ( OR=6.57, 95% CI: 3.03-14.25, P<0.001), metabolic tumor volume (MTV) ( OR=2.91, 95% CI: 1.43-5.92, P=0.003), total lesion glycolysis (TLG) ( OR=4.23, 95% CI: 2.08-8.59, P<0.001), Radscore-PET ( OR=21.93, 95% CI: 9.04-53.20, P<0.001) and Radscore-CT ( OR=13.72, 95% CI: 6.12-30.76, P<0.001) were all influencing factors for predicting lymph node metastasis in NSCLC patients. Multivariate analysis showed that, tumor marker levels ( OR=2.55, 95% CI: 1.11-5.90, P=0.028), vacuolar sign ( OR=0.26, 95% CI: 0.08-0.83, P=0.023), SUV max ( OR=5.94, 95% CI: 1.99-17.75, P=0.001), Radscore-PET ( OR=25.51, 95% CI: 5.92-110.22, P<0.001), and Radscore-CT ( OR=8.68, 95% CI: 2.73-27.61, P<0.001) were independent influencing factors for predicting lymph node metastasis in patients with NSCLC. Based on the above independent influencing factors, models were constructed: the traditional model (tumor marker levels, vacuolar sign, SUV max), the PET model (SUV max, Radscore-PET), the CT model (vacuolar sign, Radscore-CT), and the combined model (tumor marker levels, vacuolar sign, SUV max, Radscore-PET, Radscore-CT). ROC curve analysis showed that, the area under curve (AUC) of the traditional, PET, CT, and combined models in the training set were 0.75 (95% CI: 0.67-0.82), 0.90 (95% CI: 0.84-0.95), 0.85 (95% CI: 0.78-0.90), and 0.94 (95% CI: 0.88-0.97), respectively. The predictive value of the combined model was higher than that of the traditional model ( Z=5.01, P<0.001), the PET model ( Z=1.99, P=0.047), and the CT model ( Z=3.25, P=0.001). In the validation set, the AUCs for the traditional model, PET model, CT model, and combined model were 0.65 (95% CI: 0.52-0.77), 0.86 (95% CI: 0.74-0.93), 0.85 (95% CI: 0.73-0.93), and 0.90 (95% CI: 0.80-0.96), respectively. The predictive value of the combined model was superior to that of the traditional model ( Z=3.23, P=0.001). The sensitivity and specificity of the combined model in the training set were 84.37% and 91.03%, while in the validation set, the sensitivity and specificity were 82.61% and 94.74%, respectively. Calibration curves showed a good agreement between the predicted and actual probabilities in both the training and validation sets. DCA showed that the combined models had good discriminative ability in both the training and validation sets. Conclusions:Tumor marker levels, vacuolar sign, SUV max, Radscore-PET, and Radscore-CT are all independent influencing factors for predicting lymph node metastasis in patients with NSCLC. The combined model based on these factors demonstrates excellent predictive performance and clinical application value for predicting lymph node metastasis in NSCLC.

Objective To explore the surgical treatment strategy for patients with thyroid cancer complicated with primary hyperparathyroidism(PHPT).Methods A retrospective analysis was conducted on the case data of thyroid cancer patients who underwent surgical treatment at Beijing Friendship Hospital,Capital Medical University from January 2016 to January 2022.Among them,22 patients with PHPT were included in study group,and 44 patients were randomly selected from thyroid cancer patients during the same period at a ratio of 1∶2 and included in control group.The operation time,intraoperative blood loss,hospital stay and occurrence of complications of two groups of patients were compared.Results The operation time of patients in study group was significantly longer than that in control group(P＜0.01).There was no statistically significant difference in intraoperative blood loss and hospital stay between two groups of patients(P＞0.05).There were 5 cases of temporary hypocalcemia in study group,12 cases of temporary hypocalcemia and 1 case of incision infection in control group.There was no statistically significant difference in incidence of postoperative complications between two groups of patients(P＞0.05).Conclusion Thyroid cancer complicated with PHPT increases the complexity of treatment.Through adequate preoperative diagnosis and reasonable surgical treatment strategies,the risks of secondary surgery and postoperative complications can be effectively reduced,and the prognosis of patients can be improved.

AIM To explore the clinical effects of Modified Shashen Maidong Decoction combined with western medicines on patients with pediatric Mycoplasma pneumoniae pneumonia due to Yin Deficiency and Lung Heat Pattern.METHODS Ninety-eight patients were randomly assigned into control group(49 cases)for 7-day administration of Cefuroxime and Minocycline Hydrochloride,and observation group(49 cases)for 7-day administration of Modified Shashen Maidong Decoction,Cefuroxime and Minocycline Hydrochloride.The changes in symptom relief time,inflammatory factors(CRP,IL-6,TNF-α),blood gas indices(SaO2,PaO2,PaCO2),T lymphocyte subsets(CD3+,CD4+,CD8+),TCM syndrome scores,pulmonary function indices(PEF,FVC,FEV1)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated shorter symptom relief time(P＜0.05).After the treatment,the two groups displayed decreased inflammatory factors,PaCO2,CD8+,TCM syndrome scores(P＜0.05),and increased SaO2,PaO2,CD3+,CD4+(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with pediatric Mycoplasma pneumoniae pneumonia due to Yin Deficiency and Lung Heat Pattern,Modified Shashen Maidong Decoction combined with western medicines can safely and effectively improve clinical symptoms and lung functions.

With the development of precision medicine and molecular pathology, fluorescence in situ hybridization (FISH) technology has been widely promoted and applied in department of pathology. In FISH detection, the most commonly used probes are HER2 amplification probes and a variety of separation probes. When detecting pathological specimens using separation probes, some specimens may show atypical signals other than the typical red-green separation signals. The observation, understanding and interpretation of atypical signals may affect the results of FISH, which are related to molecular subtyping and drug treatment of the patient. Eight types of atypical signals of separation probes in FISH detection based on reading experience were summarized and analyzed. At the same time, this article provides evidence and analysis on whether the gene has been rearrangedthrough verification experiments, image analysis and experimental analysis in literature, aiming to enhance the understanding of readers to atypical signals of FISH separation probes.

Objective:To explore the prognostic value of a combined model of baseline 18F-FDG PET/CT tumor metabolic parameters and clinical factors for predicting progression-free survival (PFS) in Hodgkin′s lymphoma (HL). Methods:From January 2014 to May 2023, 171 HL patients (102 males, 69 females; median age 40 years) who underwent 18F-FDG PET/CT before treatment at the First Affiliated Hospital of Nanjing Medical University and Nanjing Drum Tower Hospital were retrospectively collected. HL patients from the First Affiliated Hospital of Nanjing Medical University were classified as the training set (101 patients) and HL patients from Nanjing Drum Tower Hospital were classified as the validation set (70 patients). Clinical factors and tumor metabolic parameters associated with PFS were determined by multivariate Cox regression analysis, and then the combined model and the independent model of each factor were constructed respectively. The consistency index (C-index) and AUC were used to evaluate the predictive efficacy of models, and nomogram was constructed based on the optimal model, and calibration curves were used to assess the goodness of fit of the models. The differences in Kaplan-Meier survival curves of the high-risk and low-risk groups were compared using log-rank test. Results:The multivariate Cox regression analysis indicated that the independent prognostic factors associated with PFS were the Lugano staging (hazard ratio ( HR)=3.10, 95% CI: 1.17-8.23, P=0.023), total metabolic tumor volume (TMTV) ( HR=2.65, 95% CI: 1.23-5.74, P=0.014), and maximum distance between tumors ( Dmax) ( HR=2.23, 95% CI: 1.02-4.85, P=0.044). These factors were used to construct the combined model, with the highest prognostic efficacy of the C-index for the training and validation sets of 0.692 and 0.653, and the AUC of 0.732 and 0.697, respectively. The calibration curves demonstrated that the predictions made by the combined model were in high agreement with the actual results in both the training and validation sets. The Kaplan-Meier analysis revealed a significantly lower PFS rate in the high-risk group compared to the low-risk group both in training and validation sets ( χ2 values: 5.88 and 4.52, P values: 0.015 and 0.033). Conclusion:The combined model incorporating tumor metabolic parameters and clinical factors improves prognostic efficacy in predicting PFS in HL patients.

Objective:To explore the value of baseline 18F-FDG PET/CT metabolic parameters and related clinical factors in the prognostic assessment of patients with angioimmunoblastic T-cell lymphoma (AITL). Methods:From July 2013 to December 2023, 70 patients with AITL (44 males, 26 females, age (63.9±9.6) years) from Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University (32 cases) as well as the First Affiliated Hospital of Nanjing Medical University (38 cases) who were diagnosed pathologically and underwent PET/CT imaging prior to treatment were retrospectively analyzed. PET/CT metabolic parameters (calculated using the 41%SUV max threshold method) and related clinical factors were collected. The optimal cut-off values of metabolic parameters were determined by using the ROC curve analysis. Cox proportional risk regression models were used for prognostic analyses, prediction models were constructed and efficacies were assessed by calibration curves and time-dependent ROC curves. Results:With the follow-up of 19.0(10.0, 33.3) months, disease progression or recurrence occurred in 51 patients, and 28 patients died. ROC curves showed that the optimal cut-off values on diagnosing AITL of total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), and SUV max were 767.1cm 3, 2159.6g and 13.0, respectively. TMTV (hazard ratio ( HR)=0.485, 95% CI: 0.252-0.935, P=0.031) and gender ( HR=0.441, 95% CI: 0.236-0.824, P=0.010) were independent risk factors for progression-free survival (PFS); TMTV ( HR=0.422, 95% CI: 0.178-0.997, P=0.049) and treatment regimen ( HR=0.346, 95% CI: 0.154-0.777, P=0.010) were independent risk factors for overall survival (OS). Time-dependent ROC curves indicated that the combined model of TMTV combining gender or treatment regimen had better prognostic results in predicting PFS (AUCs: 0.67-0.82) or OS (AUCs: 0.62-0.80) in patients with AITL. The calibration curve showed the predicted values of the combined models were in good consistency with the actual values. Conclusions:The metabolic parameter TMTV is an independent risk factor for PFS and OS in patients with AITL. The combined model of TMTV combining gender or treatment regimen can effectively improve the prognostic prediction efficacy of PFS or OS in patients with AITL.

BACKGROUND:According to existing clinical studies,vertebroplasty treatment with both the external pedicle approach and the pedicle approach can improve the pain and quality of life of patients with spinal compression fractures.Compared with the pedicle approach,the external pedicle approach has a freer puncture angle,and good bone cement dispersion effect can be obtained by adjusting the puncture angle. OBJECTIVE:To compare the impact of vertebroplasty through individualized unilateral external pedicle approach and bilateral pedicle approach on the treatment of spinal compression fractures by quantifying the dispersion effect of bone cement. METHODS:A total of 80 patients with thoracolumbar compression fracture were divided into two groups by random number table method.The bilateral pedicle group(n=40)underwent vertebroplasty through a bilateral pedicle approach,while the unilateral external pedicle group(n=40)underwent individualized vertebroplasty through a unilateral external pedicle approach.Anteroposterior and lateral X-rays of the affected vertebrae from two groups of patients were photographed to assess effect and type of bone cement dispersion within 3 days after surgery.Visual analog scale score,tenderness threshold around fracture,and Oswestry dysfunction index were assessed before,1,7 days,and 1 month after surgery. RESULTS AND CONCLUSION:(1)Dispersion effect of bone cement in unilateral external pedicle group was better than that in bilateral pedicle group(P<0.001),and the amount of bone cement perfusion was higher than that in bilateral pedicle group(P<0.001).In the bilateral pedicle group,the bone cement dispersion types were mainly concentrated in type Ⅰ and type Ⅲ,while in the unilateral external pedicle group,the bone cement dispersion types were mainly concentrated in type I and type Ⅱ,and there was a significant difference in bone cement dispersion types between the two groups(P<0.001).(2)Postoperative visual analog scale scores and Oswestry disability index of both groups were lower than those before surgery(P<0.001),and postoperative tenderness threshold around fracture showed a trend of decreasing first and then increasing.At the same time point after treatment,there were no significant differences in visual analog scale score,Oswestry disability index,and tenderness threshold around fracture between the two groups(P>0.05).(3)The results indicate that individualized vertebroplasty via unilateral external pedicle approach can achieve better bone cement dispersion,and the treatment effect is consistent with the vertebroplasty via classical bilateral pedicle approach.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation and joint destruction. Iguratimod (IGU) is a novel conventional synthetic disease-modifying antirheumatic drugs (csDMARD) with good efficacy and safety for the treatment of active RA in China and Japan. However, the long-term effects of IGU on the progression of bone destruction or radiographic progression in patients with active RA remain unknown. We aimed to investigate the efficacy and safety of iguratimod (IGU), a combination of methotrexate (MTX) and IGU, and IGU in patients with active rheumatoid arthritis (RA) who were naïve to MTX. METHODS: This multicenter, double-blind, randomized, non-inferiority clinical trial was conducted at 28 centers for over 52 weeks in China. In total, 911 patients were randomized (1:1:1) to receive MTX monotherapy (10-15 mg weekly, n = 293), IGU monotherapy (25 mg twice daily, n = 297), or IGU + MTX (10-15 mg weekly for MTX and 25 mg twice daily for IGU, n = 305) for 52 weeks. The patients' clinical characteristics, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), disease activity score in 28 joints-C-reactive protein (DAS28-CRP) level, and disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) were assessed at baseline. The primary endpoints were the proportion of patients with ≥20% improvement according to the American College of Rheumatology (ACR20) response and changes in the van der Heijde-modified total Sharp score (vdH-mTSS) at week 52. RESULTS: The proportions of patients achieving an ACR20 response at week 52 were 77.44%, 77.05 %, and 65.87% for IGU monotherapy, IGU + MTX, and MTX monotherapy, respectively. The non-inferiority of IGU monotherapy to MTX monotherapy was established with the ACR20 (11.57%; 95% confidence interval [CI], 4.35-18.79%; P <0.001) and vdH-mTSS (-0.37; 95% CI, -1.22-0.47; P = 0.022). IGU monotherapy was also superior to MTX monotherapy in terms of ACR20 ( P = 0.002) but not the vdH-mTSS. The superiority of IGU + MTX over MTX monotherapy was confirmed in terms of the ACR20 (11.18%; 95% CI, 3.99-18.37%; P = 0.003), but not in the vdH-mTSS (-0.68; 95% CI, -1.46-0.11; P = 0.091). However, the difference in the incidence rates of adverse events was not statistically significant. CONCLUSIONS: IGU monotherapy/IGU + MTX showed a more favorable clinical response than did MTX monotherapy. IGU may have some clinical benefits over MTX in terms of radiographic progression, implying that IGU may be considered as an initial therapeutic option for patients with active RA. TRIAL REGISTRATION https://classic.clinicaltrials.gov/ , NCT01548001.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antirheumatic Agents/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; Chromones/adverse effects* ; Double-Blind Method ; Drug Therapy, Combination ; Methotrexate/adverse effects* ; Treatment Outcome ; Sulfonamides

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.