OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective:To investigate the value of traditional metabolic parameters, CT features and intratumoral heterogeneity parameters measured by 18F-FDG PET/CT in predicting the mutation status of the epidermal growth factor receptor (EGFR) gene in patients with adenocarcinoma. Methods:A total of 147 patients (73 males, 74 females, age (59.8±10.2) years) with pathological confirmed adenocarcinoma between January 2016 and June 2020 in the Affiliated Hospital of Jining Medical University were retrospectively included. The differences of clinical data (smoking history, tumor location and clinical stage), CT features (maximum diameter, ground-glass opacity content, lobulation, speculation, cavitation, air-bronchogram, pleural retraction and bronchial cut-off sign), 18F-FDG PET/CT traditional metabolic parameters (SUV max, SUV mean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG)) and intratumoral heterogeneity parameters ( CV, heterogeneity index (HI)) were analyzed between patients with EGFR mutation and patients with EGFR wild-type. Independent-sample t test, Mann-Whitney U test and χ2 test were used to analyze the data. Multivariate logistic regression was used to analyze the predictors of EGFR mutation. ROC curve analysis was used to evaluate the predictive value of clinical and PET/CT information. Results:Among 147 patients, 87 were with EGFR mutation and 60 were with EGFR wild-type. There were significant differences in gender (male/female), smoking history (with/without), location (peripheral lesion/central lesion), pleural retraction (with/without), SUV max, SUV mean, TLG, CV and HI ( χ2 values: 4.72-23.89, z values: from -2.31 to 5.74, all P<0.05). Multivariate logistic regression analysis showed that smoking history (odds ratio ( OR)=0.167, 95% CI: 0.076-0.366; P<0.001), pleural retraction ( OR=1.404, 95% CI: 1.115-3.745; P=0.012), SUV max ( OR=0.922, 95% CI: 0.855-0.995; P=0.003), TLG ( OR=0.991, 95% CI: 0.986-0.996; P=0.001) and HI ( OR=0.796, 95% CI: 0.700-0.859; P<0.001) were predictors of EGFR mutation. ROC curve analysis showed the AUC of HI was 0.779, with the sensitivity of 76.67%(46/60) and the specificity of 79.31%(69/87). The predictive model was constructed by combining smoking history, pleural retraction, TLG, SUV max and HI, and the AUC was 0.908, with the sensitivity of 88.33%(53/60) and the specificity of 68.97%(60/87). The difference of AUCs between HI and the predictive model was statistically significant ( z=3.71, P<0.001). Conclusion:HI can predict EGFR mutations better, and the predictive value for EGFR mutations can be enhanced when combining HI with smoking history, pleural retraction, TLG and SUV max.

Purpose::Shaping and assembling contemporary external fixators rapidly for the severe mandibular fractures remains a challenge, especially in emergency circumstance. We designed a novel external fixator that incorporates universal joints to provide the stabilization for mandibular comminuted fractures. This study aims to confirm the efficacy of this novel external fixator through biomechanical tests in vitro and animal experiments. Methods::In vitro biomechanical tests were conducted using 6 fresh canine with mandibular defect to simulate critical comminuted fractures. Three mandibles were stabilized by the novel external fixator and other mandibles were fixed by 2.5 mm reconstruction plates. All fixed mandibles were subjected to loads of 350 N on the anterior regions of teeth and 550 N on the first molar of the unaffected side. The stability was evaluated based on the maximum displacement and the slope of the load-displacement curve. In animal experiments, 9 beagles with comminuted mandibular fractures were divided into 3 groups, which were treated with the novel external fixation, reconstruction plate, and dental arch bar, respectively. The general observation, the changes in animals’ weight, and the surgical duration were recorded and compared among 3 groups. The CT scans were performed at various intervals of 0 day (immediately after the surgery), 3 days, 7 days, 14 days, 21 days, and 28 days to analyze the displacement of feature points on the canine mandible and situation of fracture healing at 28 days. The statistical significance was assessed by the two-way analysis of variance test followed by the Bonferroni test, enabling multiple comparisons for all tests using GraphPad Prism10.1.0 (GraphPad Inc, USA). Results::The outcomes of the biomechanical tests indicated that no statistically significant differences were found in terms of the maximum displacement ( p = 0.496, 0.079) and the slope of load displacement curves ( p = 0.374, 0.349) under 2 load modes between the external and internal fixation groups. The animal experiment data showed that there were minor displacements of feature points between the external and internal fixation groups without statistic difference, while the arch bar group demonstrated inferior stability. The CT analysis revealed that the best fracture healing happened in the internal fixation group, followed by the external fixation and arch baring at 28 days after fixation. The external fixation group had the shortest fixation duration (25.67 ± 3.79) min compared to internal fixation ((70.67 ± 4.51) min, p < 0.001) and arch baring ((42.00 ± 3.00) min, p = 0.046). Conclusion::The conclusion of this study highlighted the efficacy and reliability of this novel external fixator in managing mandibular fractures rapidly, offering a viable option for the initial stabilization of comminuted mandibular fractures in the setting of emergency rescue.

Vestibular compensation is an important model for developing the prevention and intervention strategies of vestibular disorders, and investigating the plasticity of the adult central nervous system induced by peripheral injury. Medial vestibular nucleus (MVN) in brainstem is critical center for vestibular compensation. Its neuronal excitability and sensitivity have been implicated in normal function of vestibular system. Previous studies mainly focused on the changes in neuronal excitability of the MVN in lesional side of the rat model of vestibular compensation following the unilateral labyrinthectomy (UL). However, the plasticity of sensitivity of bilateral MVN neurons dynamically responding to input stimuli is still largely unknown. In the present study, by using qPCR, whole-cell patch clamp recording in acute brain slices and behavioral techniques, we observed that 6 h after UL, rats showed a significant deficit in spontaneous locomotion, and a decrease in excitability of type B neurons in the ipsilesional rather than contralesional MVN. By contrast, type B neurons in the contralesional rather than ipsilesional MVN exhibited an increase in response sensitivity to the ramp and step input current stimuli. One week after UL, both the neuronal excitability of the ipsilesional MVN and the neuronal sensitivity of the contralesional MVN recovered to the baseline, accompanied by a compensation of spontaneous locomotion. In addition, the data showed that the small conductance Ca²⁺-activated K⁺ (SK) channel involved in the regulation of type B MVN neuronal sensitivity, showed a selective decrease in expression in the contralesional MVN 6 h after UL, and returned to normal level 1 week later. Pharmacological blockage of SK channel in contralateral MVN to inhibit the UL-induced functional plasticity of SK channel significantly delayed the compensation of vestibular motor dysfunction. These results suggest that the changes in plasticity of the ipsilesional MVN neuronal excitability, together with changes in the contralesional MVN neuronal sensitivity, may both contribute to the development of vestibular symptoms as well as vestibular compensation, and SK channel may be an essential ionic mechanism responsible for the dynamic changes of MVN neuronal sensitivity during vestibular compensation.
Animals ; Locomotion ; Neurons/physiology* ; Patch-Clamp Techniques ; Rats ; Vestibular Nuclei/metabolism* ; Vestibule, Labyrinth

Objective: To explore the differences in the biological effects of different expansion systems on natural killer (NK) cells, as well as the safety and preliminary clinical efficacy in the treatment of patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood cells from healthy donors were stimulated with either CD3 combined with CD52 or K562 feeder cells loaded with IL-21/4-1BB to induce NK cell expansion. Changes in the NK cell phenotype, cytokine secretion, and cytotoxicity before and after expansion were detected. We also evaluated the safety and clinical efficacy of two different expansion strategies for patients received NK infusion. Results: Compared with the CD3/CD52 monoclonal antibody amplification system, the feeder cell expansion group had a higher purity of NK cells and higher expression ratios of NK cell surface activation receptors such as DNAM-1 and NKp30, while inhibitory receptor CTLA-4 expression was low and NKG2D/CD25/CD69/ Trail/PD-1/TIM-3/TIGIT had no statistically significant differences between the groups. Further functional results showed that the expression level of KI67 in NK cells after expansion in the two groups increased significantly, especially in the feeder cell expansion group. Simultaneously, the perforin and granzyme B levels of NK cells in the feeder cell expansion group were significantly higher than in the CD3/CD52 expansion group. A retrospective analysis of eight patients who received monoclonal antibody-expanded NK cell reinfusion and nine patients with trophoblast cell-expanded NK cell reinfusion was done. The disease characteristics of the two groups were comparable, NK cell reinfusion was safe, and there were no obvious adverse reactions. Clinical prognostic results showed that in the CD3/CD52 monoclonal antibody amplification group, the MRD conversion rate was 50% (2/4) , and the feeder cell expansion group was 50% (3/6) . After 5 years of follow-up from allo-HSCT, three patients in the monoclonal antibody expansion group had long-term survival without leukemia, and the remaining five patients had died; two patients died in the feeder cell expansion group, and the other six patients had long-term survival. Six cases had GVHD before NK cell reinfusion, and GVHD did not aggravate or even relieved after NK cell reinfusion. Conclusions: Preliminary results show that the biological characteristics of NK cells with diverse expansion strategies are significantly different, which may affect the clinical prognosis of patients with recurrence or persistent minimal residual disease after HSCT. The two groups of patients treated with NK cells from different expansion strategies had no obvious adverse reactions after NK cell infusion, but efficacy still needs to be further confirmed.
Antibodies, Monoclonal/pharmacology* ; Graft vs Host Disease/metabolism* ; Hematopoietic Stem Cell Transplantation ; Humans ; Killer Cells, Natural ; Retrospective Studies ; Treatment Outcome

Objective: To investigate the clinicopathologic and molecular genetic characteristics, diagnosis, differential diagnosis, treatment and prognosis of histiocyte-rich rhabdomyoblastic tumor (HRRMT). Methods: The clinical data of two cases of HRRMT diagnosed in Fujian Provincial Hospital and Fujian University of Traditional Chinese Medicine Affiliated People's Hospital from 2020 to 2021 were collected. Histopathology and immunohistochemical (IHC) staining were used to assess morphological changes; the genetic changes were analyzed with next-generation sequencing. The relevant literature was reviewed. Results: Both cases showed well-defined solid nodules and soft masses. Microscopically, the tumors had a fibrous pseudocapsule with lymphocytic aggregation, and locally invaded the surrounding skeletal muscle tissue, and the tumor cells were fusiform to epithelioid with an intensive foamy histiocytic infiltrate. No necrosis or mitosis was observed. Immunophenotyping showed the tumor cells were positive for desmin, either one or both skeletal muscle markers (myogenin or MyoD1), and negative for h-caldesmon, ALK and SMA. The Ki-67 index was<5%. Using next-generation sequencing, one case was found to harbour KRAS (G12D) and MSH3 (Q470^*) mutations. Conclusions: HRRMT is a newly described skeletal muscle tumor with uncertain malignant potential. Its diagnosis and differential diagnosis depend on morphologic and IHC staining. No specific molecular genetics changes have been identified so far.
Biomarkers, Tumor/analysis* ; Diagnosis, Differential ; Histiocytes/pathology* ; Humans ; Molecular Biology ; Muscle Neoplasms/pathology* ; Prognosis

OBJECTIVE：To explore t he risk factors that may lead to the ineff ectiveness of using palonosetron combined with dexamethasone to prevent chemotherapy-induced nausea and vomiting （CINV），and to provide a reference for the rational choice and use of antiemetic drugs. METHODS ：In a retrospective case-control study ，871 patients who used palonosetron combined with dexamethasone to prevent CINV in a tertiary cancer hospital from 2016 to 2020 were selected as the object. Totally 32 related data such as demographic data ，living habits ，medical history ，examination information and treatment information were counted as variables. Combined with single factor regression ，multi-factor regression， likelihood ratio forward or backward stepwise 163.com regression were used to comprehensively screen the factors for many times. The standard target factors screened by stepwise E-mail：kongtiandong@126.com regression were included in the multivariate Logistic regression analysis，and the regression model was evaluated by the ROC c urve. RESULTS ：The multivariate Logistic regression model fitted well（AUC in ROC was 0.83，but 0.82 after screening ）. The results showed that there were 15 statistically significant independent influential factors ，including 12 independent risk factors ，ie. poor nutritional status （OR＝2.11，95％CI（1.05，4.22），P＝0.036）， history of gastrointestinal disease （OR＝2.76，95％CI（1.87，4.07），P＜0.001），abnormal electrolyte level （OR＝2.54，95％CI （1.74，3.69），P＜0.001），nausea and vomiting 24 h before chemotherapy （OR＝8.47，95％CI（3.28，21.91），P＜0.001），history of chemotherapy-induced vomiting （OR＝3.20，95％ CI （2.18，4.71），P＜0.001），high risk level of vomiting caused by chemotherapy（OR＝3.16，95％CI（2.38，4.20），P＜0.001），application of opioid combined with non-steroidal analgesics （OR＝ 4.18，95％CI（2.06，8.49），P＜0.001），the use of other drugs that stimulate the intestine and stomach （OR＝2.49，95％CI（1.28， 4.83），P＝0.007），history of surgery （OR＝1.88，95％CI（1.34，2.63），P＜0.001），high level of albumin （OR＝1.05，95％CI （1.01，1.08），P＝0.015），multiple days of single chemotherapy （OR＝1.69，95％CI（1.11，2.56），P＝0.014），and opioid analgesia medicine （OR＝1.71，95％CI（1.15，2.53），P＝0.007）；and the following 3 independent protective factors included long time of diagnosis （OR＝0.65，95％CI（0.46，0.93），P＝0.019），non-first chemotherapy （OR＝0.52，95％CI（0.33，0.83），P＝ 0.006），and drugs combined chemotherapy （OR＝0.55，95％CI（0.34，0.90），P＝0.018）. CONCLUSIONS ：Patients with the following conditions are more likely to experience CINV prevention ineffectiveness ，ie. single long-term chemotherapy ，application of chemotherapy plan with a higher risk of emesis ，history of chemotherapy-induced vomiting ，history of gastrointestinal diseases ， nausea and vomiting 24 hours prior to chemotherapy ，history of surgery ，within 1 year of diagnosis ，chemotherapy for the first time，use of opioids ，use of 5-HT3 reuptake inhibitors ，malnutrition and electrolyte disorders.

Objective:To evaluate the diagnostic value of contrast-enhanced ultrasound(CEUS) in renal atypical space occupying lesions.Methods:The images of conventional ultrasound and CEUS in 44 patients with 47 renal atypical space occupying lesions from May 2015 to June 2019 were retrospectively analyzed, including 26 males and 18 females. The mean age of patients was(55.9±13.7)years old, ranged from 27 to 79 years old. The mean size of the lesions in conventional ultrasound was (2.5±1.3)cm, ranged from 1.0 to 6.0 cm. The location, size, echo, boundary and color flew signals of renal lesions were observed by conventional ultrasound.The degree and the pattern of enhancement, presence or absence of a clear capsule sign were analyzed by CEUS. The ultrasound diagnosis results were compared with the pathological or clinical diagnosis.Results:Of the 47 lesions, 15 were malignant and 32 were benign. 19 lesions were diagnosed by operation pathology, including 13 renal cell carcinomas, 2 renal lymphomas, 3 renal cysts and 1 inflammatory granuloma; the other 28 benign tumors or pseudotumors were diagnosed by enhanced CT or MRI, and were followed up for more than 1 year, including 5 angiomyolipomas, 15 cysts, 3 renal junction cortex defects, 2 renal column hypertrophies, 1 local non-atrophic renal parenchyma, 1 hump kidney and 1 scar. Most of the renal cell carcinomas were hypoechoic (8/13), "fast wash-in and fast wash-out " (9/13), heterogeneous hypoenhancement (6/13), 9 with pseudocapsule and 6 with necrosis. 2 renal lymphomas were hypoechoic, "fast wash-in and fast wash-out" , 1 isoenhancement and 1 hypoenhancement. The angiomyolipomas were hyperechoic, "slow wash-in and slow wash-out" (4/5), 2 hypoenhancement, 2 hyperenhancement and 1 isoenhancement. Most renal cysts were anechoic(16/18). There was no enhancement in simple renal cysts. The wall or septum of complex renal cysts was thin and homogeneous enhanced, showing "slow wash-in and slow wash-out" with isoenhancement or hypoenhancement. Inflammatory granuloma was cystic-solid. The solid part was hypoenhancement. Renal column hypertrophy, hump kidney and local non-atrophic renal parenchyma were hypoechoic, showing the same enhancement pattern as renal parenchyma by CEUS. The junctional parenchyma defect and renal scar were hyperechoic, showing no enhancement. The sensitivity, specificity, accuracy and the area under the ROC curve of conventional ultrasound and CEUS in the diagnosis of benign and malignant lesions were 86.7%, 87.5%, 87.2%, 0.871 and 100.0%, 96.9%, 97.9%, 0.984.There were significant differences in the diagnosis of renal atypical space occupying lesions between two methods ( P=0.03). Conclusions:CEUS was better than conventional ultrasound in the diagnosis of renal atypical space occupying lesions. CEUS had advantages in the differential diagnosis of benign and malignant tumors, benign lesions and anatomical variants mimicking a renal tumor.

【Objective】 To explore the regulation and mechanism of mannose(Man) on inflammatory response, so as to provide the basis for application of Man in inflammatory diseases. 【Methods】 RAW264.7 macrophages were treated with different concentrations of Man for 24 h or 48 h, and the proliferation was detected by cell count. RAW264.7 cells were pretreated with low concentration(2 mmol/L) and high concentration(20 mmol/L) of Man for 12 h, followed by treatment with lipopolysaccharide(LPS) for 8 h or 24 h more. mRNA, protein and culture supernatant were collected, and the inflammation related cytokines, proteins and mannose receptor(CD206) were detected by Q-PCR, Western blot, and ELISA. 【Results】 The cell proliferation was increased with the increase of Man concentration under 5 mmol/L, while it was decreased with the increase of Man concentration over 5 mmol/L. Compared with LPS treatment, 2 mmol/L mannose(Man2) plus LPS increased the mRNA levels of IL-1β, IL-12 and TNF-α and the protein levels(all P<0.05), while Man20 + LPS treatment significantly decreased the mRNA levels of IL-1β, IL-12, TNF-α, IL-6, and CCL2 and the protein levels (all P<0.05). The potential targets of network pharmacology for Man and its metabolites were 20 proteins, including AKT and STAT3. Furthermore, the phosphorylation levels of AKT and STAT3(all P<0.05) were increased in Man2 + LPS group and the phosphorylation levels of AKT, p65 and ERK(all P<0.05) were decreased in Man20 + LPS group compared with LPS group. The phosphorylation levels of AKT, p65 and STAT3(all P<0.05) were decreased in Man20 group compared with control group. 【Conclusions】 Different concentrations of mannose have various effects on inflammatory response. Low concentration mannose promotes macrophage inflammatory response induced by LPS, while high concentration mannose inhibits LPS-induced inflammatory response. And this mechanism is related to the regulation of AKT, STAT3, p65, and ERK activities.

Objective:To explore the method of noninvasive hemodynamic monitoring system (NICaS) in monitoring the hemodynamics of patients with acute pesticide poisoning, and to analyze the clinical guiding value of NICaS in hemodynamics of patients with severe pesticide poisoning.Methods:In August 2019, 200 patients with severe acute organophosphorus pesticide poisoning (AOPP) or moderate severe acute paraquat pesticide poisoning (APP) admitted to Harrison international peace hospital from January 2017 to August 2019 were randomly divided into NICaS group ( n=68) , transpulmonary thermodilution method ( n=67) and empirical treatment group ( n=65) . The relationship between acute physiology and chronic health score (APACHE Ⅱ) , heart rate, hemodynamic indexes, survival rate and complications were analyzed. Results:There were no significant differences in age, sex ratio, body mass index, heart rate, systolic blood pressure, no treatment period and admission APACHE II score between NICaS group, Picco group and experience group ( P>0.05) ; Compared with the experience group, the mortality of AOPP and app in NICaS group and Picco group were lower, and the differences were statistically significant ( P<0.05) .The cardiac output (CO) had a significant correlation in the interval of 2.8-6.7 L·min -1 ( r=0.738, r2=0.545, P<0.01) , and peripheral vascular resistance index (SVRI) had a significant correlation in the interval of 410-1 950 d·s·cm -5·m 2 ( r=0.792, r2=0.627, P<0.01) . Bland Altman analysis showed that CO and SVRI measured by Picco and NICaS had 97.01% and 95.52% consistency, respectively. Compared with the experience group, the average daily infusion volume and daily colloid infusion volume of NICaS group and Picco group were lower, the differences were statistically significant ( P<0.05) . Conclusion:NICaS can effectively monitor the hemodynamic indexes of patients with acute pesticide poisoning.