OBJECTIVETo assess the therapeutic efficacy and safety of Kunxian Capsule (KXC) in treatment of rheumatoid arthritis (RA).

METHODSRandomized positive parallel controlled and multi-center open test method was adopted. 240 RA patients of mild/moderate degree were randomly assigned to three groups equally, i.e., KXC group (who took KXC), the methotrexate (MTX) group (who took MTX), and the KXC + MTX group (who took KXC and MTX simultaneously), respectively. The therapeutic course for them all was 12 weeks. The effect of the treatment was assessed in items of DAS28, ACR20, and ACR50; number of joints with pain and swelling; VAS score of pain, tiredness, and general condition; time of morning stiffness; bilateral grip strength; HAQ score, as well as blood levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-CCP antibody, and platelet count.

RESULTSBy the end of the 4th week, the improvement of ACR20, ACR50, DAS28 efficacy judgment, and DAS28 score in the KXC + MTX group were much better than those in the other two groups, with statistical difference (P<0.05). The total effective rate was 88. 6% and the markedly effective rate was 51.8% in the KXC + MTX group at the 12 th week. The Improvement was more obviously shown in all groups after treatment (all P<0.05). Better effects in reducing VAS scores of pain and tiredness were shown in the KXC group and the KXC + MTX group. The effects of KXC + MTX were superior to the other two groups in terms of swollen joint numbers, pain joints, grip strength (assessed by researcher), as well as VAS score of general condition and HAQ score (assessed by both patients and researcher, P<0.05). But the differences among groups in improving morning stiffness and the incidence rate of adverse events were in- significant.

CONCLUSIONSKXC could relieve symptoms, improve joint functions, physical signs, and laboratory indices of RA patients with less adverse reaction. It was synergistic with MTX.

Adult ; Antirheumatic Agents ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; Drug Synergism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Methotrexate ; therapeutic use ; Middle Aged ; Phytotherapy ; Treatment Outcome

Curcumin has a wide spectrum of pharmaceutical properties such as antitumor, antioxidant, antiamyloid, and anti-inflammatory activity. However, poor aqueous solubility and low bioavailability of curcumin are major challenge in its development as a useful drug. To overcome many of these problems, curcumin-loaded long-circulating liposomes (Cur-LCL) were prepared by the ethanol injection method. Morphology of Cur-LCL was observed by transmission electron microscope, mean particle size and Zeta potential were detected by laser particle size analyzer, entrapment efficiency and drug loading were evaluated by ultracentrifugation. The drug release behavior in vitro and pharmacokinetic behavior in rats of Cur-LCL were investigated with curcumin (Cur) and curcumin liposomes (Cur-Lips) as control. The results showed that the mean diameter of Cur-LCL was 110 nm, the Zeta potential was -5.8 mV. The entrapment efficiency and drug loading of Cur-LCL was 80.25%, 2.06%, respectively. The release behavior in vitro studied by dialysis in PBS buffer showed significant sustained release profile that 48.95% Cur were released from Cur-LCL in 7 h, 88.92% in 24 h. The pharmacokinetic parameters showed that compared with Cur and Cur-Lips, the t(1/2beta) of Cur-LCL was extended to 13 and 1.8-fold, respectively. Besides, the AUC values was significantly increased (P < 0.01), and the clearance was evidently decreased (P < 0.01). These results from in vitro and in vivo indicated that Cur-LCL were able to realize controlled drug release and increase circulation time.
Animals ; Curcumin ; chemistry ; pharmacokinetics ; Delayed-Action Preparations ; chemistry ; pharmacokinetics ; Drug Carriers ; chemistry ; Female ; Humans ; Liposomes ; chemistry ; Male ; Particle Size ; Rats ; Rats, Sprague-Dawley ; Solubility

OBJECTIVESThe mutations of growth hormone receptor (GHR) gene results in growth hormone insensitivity (Laron syndrome) or partial growth hormone insensitivity. This study aimed to understand the relation between mutations of GHR gene and short stature with non-growth-hormone deficiency, and the clinical feature of the patients with the GHR gene mutations.

METHODS(1) Forty-seven patients with non-growth-hormone deficiency and short stature were enrolled in this study, 33 were male and 14 female. The age of the patients were at a range of 2 - 16 years. (2) The mutations of GHR gene were identified by PCR-SSCP and DNA sequencing. (3) The characteristics of the GHR mutation was assumed by screening for the same mutations in patients' family members and the control samples.

RESULTS(1) Four GHR mutations were identified in 5 patients with non-growth-hormone deficiency: H56R, G148E, IVS6-30, -31CA > TG and IVS8 + 10G > C. These mutations were located within the extracellular domain of GHR and not reported before. Five patients were the heterozygous of H56R, G148E, IVS6-30, -31CA > TG and IVS8 + 10G > C. The detection rate of mutant heterozygous individual accounted for 10.6% (5/47). The mutations were considered non-polymorphism by the GHR gene analysis in patients' family members and control samples. (2) Comparison of the amino acid sequence of different species and the position of the mutations H56R and G148E in the GHR protein structure suggested impact of the mutations on the protein function. (3) A polymorphism site was identified in exon 6 of GHR gene: G168G (GGA > GGG). The allelic frequency of G168G had no difference between the patients with non-growth-hormone deficiency and control samples but had significant difference between Chinese and Caucasian. It seems that the G168G was a polymorphism and has no relationship with the height stature. However, there was the allele diversity in different races.

CONCLUSIONThe mutations of GHR gene were detected in the patients with non-growth-hormone deficiency. Special attention should be paid clinically to its potential pathogenesis for short stature.

Adolescent ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Case-Control Studies ; Child ; Child, Preschool ; DNA Mutational Analysis ; European Continental Ancestry Group ; genetics ; Female ; Growth Disorders ; genetics ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Polymorphism, Genetic ; Receptors, Somatotropin ; genetics

OBJECTIVETo investigate the usefulness of (18)F-FDG PET/CT imaging in restaging, evaluating the treatment outcome, monitoring relapse and predicting prognosis of T-cell lymphoma.

METHODSRetrospective analysis of PET/CT image results of thirty-four patients with T-cell lymphoma, and to evaluate its clinical significance in restaging, treatment efficiency, relapse monitor and prognosis prediction.

RESULTSClinical restaging among the 20 stage I and II patients, 6 were ascended, 9 descended and 5 unchanged. Restaging among the other 14 stage III and IV patients, 3 were ascended, 4 descended and 7 unchanged. There were 12 patients in complete remission (CR), 11 in partial remission (PR), 2 in stable disease (SD) and 9 in progressive disease (PD) among all the 34 patients. There is obvious statistical difference of the standardized uptake value (SUV) between the efficacy group and the inefficacy group after treatment of 6 courses at least in 25 patients among all the 34 patients (P = 0.009). There is obvious statistical difference of the SUV value before and after treatment in 8 patients among all the 34 patients (P = 0.000). There is obvious statistical difference in the survival time between the efficacy group and the inefficacy group after treatment of 6 courses at least in 25 patients among all the 34 patients (P = 0.015).

CONCLUSIONS(18)F-FDG PET/CT imaging plays an very important role in guiding clinical restaging, evaluating the treatment outcome, monitoring relapse and predicting prognosis of T-cell lymphoma. It is helpful to establish personalized treatment planning.

Adolescent ; Adult ; Aged ; Female ; Fluorodeoxyglucose F18 ; Humans ; Lymphoma, T-Cell ; diagnostic imaging ; therapy ; Male ; Middle Aged ; Positron-Emission Tomography ; methods ; Prognosis ; Retrospective Studies ; Tomography, X-Ray Computed ; methods ; Treatment Outcome ; Young Adult

OBJECTIVETo explore the value of dual-time-point (18)F-fluorodeoxyglucose integrated positron emission and computed tomography ((18)F-FDG PET-CT) in differentiation of malignant from benign gastrointestinal diseases.

METHODSSixty five patients with suspected gastrointestinal lesions underwent dual-time-point (18)F-FDG PET-CT imaging. Standardized uptake value (SUV) was calculated for semi-quantitative assessment. The SUV of the two acquisitions were signed SUV(early) and SUV(delayed), respectively. Then the change of SUVmax (ΔSUVmax) was calculated. The ROC curves of the SUV(early), SUV(delayed) and ΔSUV were drawn to find the best cut-off point value for differential diagnosis, and then the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated, respectively.

RESULTSOf the malignant lesions, the SUVmax in delayed imaging were significantly higher than those in early imaging, while there were no significant differences of SUVmax between the two images of the benign lesions. The ΔSUVmax of the malignant lesions were significantly higher than that of the benign ones. Taking the SUVmax higher than 9.2 in early imaging as positive diagnostic criteria, the sensitivity was 72.7%, the specificity was 85.7%, the positive predictive value was 91.4%, the negative predictive value was 60.0%, and the accuracy was 76.9%. Taking the SUVmax higher than 10.9 in delayed imaging as positive diagnostic criteria, the sensitivity was 75.0%, the specificity was 90.5%, the positive predictive value was 94.3%, the negative predictive value was 63.3%, and the accuracy was 80.0%. Taking the ΔSUVmax higher than 5.1% as positive diagnostic criteria, the sensitivity was 95.5%, the specificity was 85.7%, the positive predictive value was 93.3%, the negative predictive value was 90.0%, and the accuracy was 92.3%. The accuracy of dual-time-point (18)F-FDG PET-CT imaging was significantly higher than that of single-time point (18)F-FDG PET-CT imaging.

CONCLUSIONDual-time-point (18)F-FDG PET-CT imaging is a useful method for differentiating malignant from benign gastrointestinal diseases, and it is superior to the single-time point (18)F-FDG PET-CT imaging.

Adenocarcinoma ; diagnosis ; pathology ; Adult ; Aged ; Aged, 80 and over ; Colitis ; diagnosis ; pathology ; Colorectal Neoplasms ; diagnosis ; pathology ; Diagnosis, Differential ; Female ; Fluorodeoxyglucose F18 ; Follow-Up Studies ; Gastritis ; diagnosis ; pathology ; Gastrointestinal Diseases ; diagnosis ; pathology ; Gastrointestinal Neoplasms ; diagnosis ; pathology ; Humans ; Male ; Middle Aged ; Positron-Emission Tomography ; methods ; Predictive Value of Tests ; Proctitis ; diagnosis ; pathology ; Proctocolitis ; diagnosis ; pathology ; ROC Curve ; Radiopharmaceuticals ; Sensitivity and Specificity ; Stomach Neoplasms ; diagnosis ; pathology ; Tomography, X-Ray Computed ; methods

OBJECTIVETo screen hepatocellular carcinoma (HCC) autoantibodies as diagnostic biomarkers or therapy targets by serologic proteome analysis (SERPA).

METHODSTotal proteins extracted from human HCC cell line HCCLM3 were separated by two-dimensional electrophoresis (2-DE) and then transferred onto PVDF membranes, which were subsequently incubated with sera from HCC, hepatitis B virus (HBV) infected patients or healthy volunteers. All immuno-reactive protein spots on blot films were matched to those on 2-DE gel maps by image analysis and identified by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS/MS).

RESULTS2-DE gel maps of HCCLM3 and corresponding blot films of good quality and reproducibility were established. The number of spots on HCCLM3 2-DE reference gel totaled 603 and those on HCC, HBV and healthy sera blotted films were 70.75+/-24.25, 68.5+/-23.44 and 41.38+/-15.05, respectively. Blot films of HCC and HBV groups had more spots than those of the healthy group (P < 0.05) while no significance was found between films of HCC and HBV groups. By identification, those HCC autoantibodies could be classified as nuclear proteins, cytoskeleton proteins, heat shock proteins and metabolic enzymes.

CONCLUSIONSerological proteome analysis is a high throughput technique for screening tumor autoantibodies. Those newly identified HCC associated tumor antigens and corresponding autoantibodies can be used in the early diagnosis or immuno-therapy of HCC.

Antibodies, Neoplasm ; analysis ; Autoantibodies ; analysis ; Carcinoma, Hepatocellular ; immunology ; Electrophoresis, Gel, Two-Dimensional ; Humans ; Liver Neoplasms ; immunology ; Proteomics ; methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Tumor Cells, Cultured

This study was to investigate the relationship between Clostridium difficile associated diarrhea (CDAD) and intestinal microecosystem in patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to clarify clinical characteristics of intestinal microecosystem disorder. Clostridium difficile (CD) was isolated and identified by enzyme-linked-immunosorbent assay using clostridium difficile Premier toxins A&B Kit and anaerobic culture in 44 cases with diarrhea. Fecal flora (bifidobacteria, lactobacillus, bacteroides, peptostreptococcus, Clostridium perfringens, enterobacteriaceae, enterococcus, and yeasts) of patients were quantitatively and qualitatively analyzed by Mitsuoka's methods. The results showed that CDAD occurred after using antibiotic or chemotherapy. Clostridium difficile was detected in 12 patients with diarrhea (positive rate was 27.27%). There was marked changes of intestinal microecosystem when patients suffered from CDAD. The number of lactobacillus, bifidobacteria, bacteroides, enterobacteriaceae and so on decreased significantly. It was effective to treat CDAD with vancomycin, metronidazole and probiotic, but the recurrence rate was 16.67%. In conclusion, CDAD complicated by allo-HSCT is related to change of intestinal microecosystem. While treating CDAD with the sensitive antibiotic, the intestinal flora of patients should be supported actively. This treatment contributes to improving disease status and reducing diarrhea recurrence.
Adolescent ; Adult ; Anti-Bacterial Agents ; adverse effects ; therapeutic use ; Child ; Clostridium Infections ; microbiology ; Clostridium difficile ; growth & development ; Diarrhea ; microbiology ; Female ; Hematologic Neoplasms ; therapy ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Young Adult

BACKGROUND: Previous studies have found that electroacupuncture (EA) could effectively inhibit the expression of p38 and Fas mRNA mediated by MAPK signaling pathways, to further inhibit the apoptosis of chondrocytes. Meanwhile,EA delays the degeneration of articular cartilage mediated by JAK-STAT signaling pathway through upregulating the expression levels of transforming growth factor β1 as well as the mRNA expression levels of STAT3, Smad3 and LepR.OBJECTIVE: To explore the effect of EA on the cartilage ultrastructure and mRNA expression levels of Ras, Raf,MEK1/2 and ERK1/2 in the rat with knee osteoarthritis.METHODS: The rat models of knee osteoarthritis were established, and randomized into four groups at 2 weeks after modeling: model group received no interventions; 15- and 30-minute EA groups were given EA at the Hsiyen (medical,extra) of bilateral knee joints for 15 and 30 minutes, respectively; PD98059 group was given the intravenous injection of extracellular signal-regulated kinase inhibitor PD98059. The intervention time was 3 months. Those rats received normal feeding served as blank control group.RESULTS AND CONCLUSION: Transmission electron microscopy showed that compared with the model group, the chondrocytes in the 15- and 30-minute EA and PD98059 groups changed little, the nucleus was larger, partial endoplasmic reticulum cisterna expanded, and the mitochondria structure was clear. ELISA results showed that the 15-and 30-minute EA and PD98059 groups had a significant decrease in the level of tumor necrosis factor α compared with the model group (P < 0.01). RT-PCR revealed that the mRNA expression levels of Ras, Raf, MEK1/2 and ERK1/2 in the 15- and 30-minute EA and PD98059 groups were significantly downregulated (P < 0.05 or P < 0.01). These results indicate that EA can alleviate chondrocyte injury in the rat osteoarthritic model, reduce the level of tumor necrosis factor α in the synovium, and downregulated the expression levels of Ras, Raf, MEK1/2 and ERK1/2 mRNA, further delaying the chondrocyte degeneration in osteoarthritis.

Acute pancreatitis (AP) is a common disease faced by clinicians. Severe acute pancreatitis (SAP) has a high mortality rate, so early identification of patients who may develop into SAP is of great significance for guiding treatment. Machine learning is a multi-layer representational learning algorithm that analyzes and obtains laws from existing data and uses these laws to make predictions on unknown data. This study established an SAP prediction scoring system based on machine learning, which can predict the SAP risk of patients within 24 hours. The prediction accuracy rate is as high as 87.36% and AUC 94.11%. The model can better assist clinical decision-making and treatment, and guide doctors to make relevant interventions earlier.

Objective To investigate the occurrence of adverse events of lurasidone in the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database by using Open Vigil FDA2.1,to enrich the experience and provide the basis for the clinical use of the drug in China.Methods Using Open Vigil FDA2.1,adverse event data were extracted from the FAERS database for a total of 51 quarters from the 4th quarter of 2010 to the 3rd quarter of 2023,and the ratio of reporting ratio(ROR)method and the proportional reporting ratio(PRR)method were used for data mining and analysis.Results A total of 32 728 adverse event reports with lurasidone as the first suspected drug was obtained,with a larger proportion of females(54.26％)and occurring mostly in adults(18 to 59 years).After the screening,326 preferred term(PT)signals were obtained,involving 20 system-organ classifications(injury,poisoning and procedural complications,general disorders and administration site conditions,psychiatric disorders,etc.).Among them,PTs with the higher frequency of occurrence included off label use,feeling abnormal,crying,anxiety,depression,insomnia,etc.PTs with stronger signal strength included activation syndrome,mania,tongue movement disturbance,hypoprolactinaemia,akathisia,etc.Multiple new suspected adverse drug reactions were unearthed,including hypoprolactinaemia,emotional poverty,stiff tongue,etc.Conclusion Lurasidone has a favorable safety profile,and women need to closely monitor prolactin levels when taking this medication.The drug is relatively safe for use in pregnant,puerperal and perinatal women and patients with poor metabolic function.Hypoprolactinaemia and restless leg syndrome are new rare suspected adverse events with lurasidone.