Objective To observe clinical efficacy and safety of adalimumab(ADA)injection combined with methotrexate(MTX)tablets in the treatment of patients rheumatoid arthritis(RA)and its influences on bone metabolism.Methods According to cohort method,the RA patients were divided into treatment group and control group.The control group was treated with oral MTX tablets(10 mg/once,once/week),while treatment group was given subcutaneous injection of ADA ejection(40 mg/once,once/2 weeks)on basis of control group.Both groups were treated for 24 weeks.The clinical curative effect,symptoms improvement,joint function and serum bone metabolism indexes[bone alkaline phosphatase(B-ALP),bone glaprotein(BGP),carboxyterminal propeptide of type Ⅰ procollagen(PICP)]in the two groups were compared,and safety was evaluated.Results There were 37 cases in control group and 43 cases in treatment group.After treatment,total response rates of treatment group and control group were 93.02％(40 cases/43 cases)and 75.68％(28 cases/37 cases),the difference was statistically significant(P＜0.05).After treatment,morning stiffness time in treatment group and control group were(29.27±7.05)and(48.63±12.25)min,the number of joint swelling were 2.64±0.66 and 4.04±1.09,number of joint tenderness were 4.51±1.12 and 6.23±2.07,levels of serum B-ALP were(20.76±2.82)and(26.41±3.05)U·L-1;levels of serum BGP were(27.45±3.41)and(23.86±3.17)ng·mL-1;levels of serum PICP were(47.39±5.63)and(41.68±5.24)ng·mL-1,the differences were statistically significant(P＜0.05).The adverse drug reactions in treatment group were mainly on headache,pruritus at the injection site,diarrhea and nausea,while which in control group were mainly on diarrhea,anorexia and nausea.The difference in incidence of adverse reactions between treatment group and control group was not statistically significant(11.63％vs 8.11％,P＞0.05).Conclusion Clinical curative effect of ADA injection combined with MTX tablets is significant in RA patients,which can significantly relieve clinical symptoms,promote recovery of joint function,reduce levels of serum rheumatoid factor,relieve inflammatory response and improve bone metabolism.

Objective To investigate the effect of rapid ultrasonic tissue processing on breast biopsy tissue.Methods Totally 100 breast puncture samples from the Department of Pathology at Shengjing Hospital of China Medical University in 2023 were randomly selected and dehydrated using rapid ultrasound tissue processing technology(the rapid group).Paired surgical samples(0.3 cm×0.3 cm×0.3 cm)that did not undergo neoadjuvant therapy before surgery were collected and subjected to routine pathological tissue treat-ment(the conventional group).The two groups of samples were subjected to routine sectioning after dehydration.The dehydration time,hematoxylin and eosin(HE)staining effect,and fluorescence in situ hybridization(FISH)results of the two groups were compared.Next,the estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER2)immunohistochemical(IHC)detection results of the two groups were compared using the kappa test with paired counting data.Results Dehydration time in the rapid group(46.70±1.42 min)was significantly shorter than that in the conventional group(659.25±6.03 min,t=987.44,P<0.001).No significant differences were observed between the HE staining scores of the rapid group(10.13±1.12)and that of the conventional group(10.15±0.97).The consistency rate of ER expression between the two groups was 92.5%(Kappa=0.794,P<0.05),that of PR expres-sion between the two groups was 76.25%(Kappa=0.639,P<0.05),and that of HER2 expression between the two groups was 72.5%(Kappa=0.610,P<0.05).The FISH results were consistent between the two groups.Conclusion Rapid ultrasonic tissue treatment has the advantages of a short procedure time,less pollution,and simple operation.The present study showed no statistically significant differences between the effect of rapid tissue treatment on tissue sections and that of routine dehydration.Therefore,this method can be widely used in pathology for the analysis of small samples.

OBJECTIVES: To establish a carbofuran intragastric administration death model in rabbits, and to observe the postmortem distribution and postmortem redistribution of carbofuran-7-phenyl glucuronic acid (Glu-7PH) in rabbits. METHODS: The postmortem distribution: Rabbits were given an administration of 1/2LD50, LD50, 2LD50 carbofuran. Dead rabbits were dissected immediately. Rabbits that had remained alive 2 hours were sacrificed by carbon dioxide (CO₂) inhalation and dissected immediately. The myocardium, cardiac blood, liver, spleen, lung, kidney, brain and right hindlimb muscle were collected. The postmortem redistribution: After giving an administration of 4LD50 carbofuran, the myocardium, cardiac blood, liver, spleen, lung, kidney, brain, and right hindlimb muscle were collected at 0, 12, 24, 48, and 72 h postmortem in supine position at 15 ℃ room temperature. The quantity of Glu-7PH was determined by LC-MS/MS. RESULTS: The postmortem distribution: Among the three dose groups, there were significant differences in the quantities of Glu-7PH in different tissues. The postmortem redistribution: There was no significant difference in the Glu-7PH quantities in cardiac blood, mycardium, spleen, kidney, brain and right hindlimb muscle, but there was a significant difference in the Glu-7PH quantities in the liver and lung. CONCLUSIONS The mycardium, cardiac blood, liver, lung, kidney, brain and hindlimb muscle of rabbits can be used as appropriate samples for Glu-7PH detection. However, it should be noted that Glu-7PH was redistributed postmortem in rabbit liver and lung.
Animals ; Rabbits ; Carbofuran ; Chromatography, Liquid ; Postmortem Changes ; Tandem Mass Spectrometry ; Autopsy

The mucous barrier is a major physiological obstacle that the mucosal drug delivery system needs to deal with. In response to this physiological barrier, many achievements have been made in research of mucosal adhesion and mucus penetration. This review puts emphasis on the progress of the research on new mucosal adhesion strategies such as cationization, sulfhydrylization, maleimide functionalization, lectinization and catechol conjugation; polyethylene glycol (PEG), polyvinyl alcohol (PVA), poly (2-alkyl-2-oxazoline) (POZ), zwitterionic polymers and other mucus-inert materials, strategies to enhance mucus penetration ability such as enzyme functionalization, reducing agent pretreatment and so on. The problems of each strategy are also analyzed and discussed, which can provide some references for clinical transformation.

The water-soluble polypeptide drug oxytocin was encapsulated in liposomes by reverse-phase evaporation vesicle method to obtain oxytocin loaded liposomes (OT@LPs) which was further modified with cationic cell penetrating peptide—arginine octamer (R8) to get R8 modified oxytocin loaded liposomes (OT@LPs-R8) which showed enhanced mucoadhesive. The brain targeting efficiency was evaluated preliminarily after nasal administration. OT@LPs-R8 showed a round shape with a particle size distribution of 110.2 ± 7.3 nm, a surface potential as high as +18 mV, a drug loading (62.17 ± 1.88) %, an encapsulation rate (5.85 ± 0.72) %, and stood stable in nasal mucus. After nasal administration, it could significantly prolong the retention and enhance the distribution in the brain with no irritation to the nasal mucosa. The animal experiment in line with the regulations of the Department of Laboratory Animal Science of Fudan University on the ethics of animal experiments had been carried out after passing the review of the Animal Ethics Committee of Fudan University. The results showed nasal administration of OT@LPs-R8 could promote oxytocin directly into the brain from the nose which expected to become a new carrier for delivery of oxytocin to the brain.

Xiaoshuan Tongluo formula is effective in treating mental retardation and speech astringency caused by cerebral thrombosis, but its mechanism remains unclear. In this investigation, by collecting the chemical constituents from Xiaoshuan Tongluo formula and the targets related to stroke, we obtained 1 251 constituents from the formula and 10 drug targets related with stroke. We established 18 prediction models of compound-target interaction for 10 stroke-related targets, using molecular docking method and machine learning methods includes Naive Bayesian and recursive partitioning based on the input of molecular fingerprints and molecular descriptors. Using these models, we predicted the active chemical constituents from Xiaoshuan Tongluo formula and their drug targets, 153 potential active constituents were discovered, 22 among them could interact with at least two drug targets related with stroke. On this basis, the chemical constituent-target network was constructed using network construction software, and then the important metabolic pathways of the targets were identified by using Gene-Ontology (GO) enrichment analysis, such as blood coagulation, positive regulation of angiogenesis, positive regulation of ion transport and so on. On this basis, a target-pathway network was constructed. In conclusion, using machine learning, molecular docking, virtual screening, data mining and network construction, this study explored and partially revealed the active chemical constituents and chemical constituent-target-pathway network action mechanism of Xiaoshuan Tongluo formula against stroke, which will provide important information for its further study.

Objective To investigate the application and advantages of alternative vascular hemihepatic occlusion in anatomic mesohepatectomy.MethodsThe clinical data of 57 patients with liver cancer who underwent operation in hepatobiliary surgery of Fuzhou general hospital from January 2014 to December 2017 were retrospectively analyzed.According to the surgery method, the patients were divided into observation group and control group, 34 cases in observation group were performed anatomic mesohepatectomy with alternative hemihepatic occlusion, 23 cases in control group were treated with non-anatomical liver lobectomy.The clinical effect of two groups were compared.Results The observation group was significantly better than the control group in terms of operation time, intraoperative blood loss, length of hospital stay, hospitalization costs, ALB at 1, 3, 5 days after surgery, ALT and AST at 1, 3, 5, 7 days after surgery, the differences were significant (P＜0.05).There was no perioperative deaths in the two groups.ConclusionApplied alternative hemihepatic vascular occlusion in anatomic mesohepatectomy can achieve good short-term curative effect and high safety.

To investigate the effect of controlled hypotension by urapidil on the predictive accuracy and diagnostic threshold of stroke volume variation (SVV) in hypertensive and non-hypertensive patients undergoing robotic hepatobiliary surgery.
 Methods: Eighty patients undergoing robotic hepatobiliary surgery under general anesthesia were divided into a hypertension group (n=25) and a non-hypertension group (n=38) according to whether or not essential hypertension was present (excluding some cases that didn't meet requirements). The pump speed was at 6.0-7.0 µg/(kg﹒min), and the range of hypotension was between 10%≤Δ systolic blood pressure (SAP)≤20%. Volume loading test was performed after artificial pneumoperitoneum was established in reverse-Trendelenburg position. Hemodynamic indexes including heart rate (HR), SAP, cardiac output (CO), cardiac index (CI), stroke volume (SV), stroke volume index (SVI) and SVV were recorded before and after infusion. Then the receiver operating characteristic (ROC) curves of SVV was drawn to determine the accuracy and diagnosis of SVV in predicting volume status in hypertensive and non-hypertensive patients after anti-Trendelenburg posture and pneumoperitoneum.
 Results: In the patients with controlled hypotension by urapidil, the area under the ROC curve of SVV in the hypertension group was 0.974, the diagnostic threshold was 13.5%, the ROC curve of SVV in the non-hypertension group was 0.832, and the diagnostic threshold was 15.5%.
 Conclusion: SVV can accurately predict the volume status in the hypertension group and the non-hypertension group after controlled hypotension in the anti-Trendelenburg position and fixed pneumoperitoneal pressure, and the SVV diagnostic threshold in the non-hypertensive group is higher than that in the hypertensive group.
Biliary Tract Diseases ; surgery ; Blood Pressure ; Cardiac Output ; Fluid Therapy ; Hemodynamics ; Humans ; Hypotension, Controlled ; Liver Diseases ; surgery ; ROC Curve ; Robotic Surgical Procedures ; Stroke ; Stroke Volume

Objective To assess the feasibility of using 28S ribosomal RNA （28S rRNA） and mitochondrial cytochrome c oxidase subunit Ⅰ （COⅠ） gene sequences of nine necrophagous Calliphorid flies for the identification of common necrophagous Calliphorid flies, and to provide technical support for postmortem interval （PMI） estimation. Methods Twenty-three Calliphorid flies were collected and identified morphologically, and DNA were extracted from legs. The gene fragments of 28S rRNA and COⅠ were amplified and sequenced, then the sequence alignment was performed with BLAST. The composition of obtained sequences was analyzed and evolutionary divergence rate between species and intraspecies were established. The phylogeny tree was constructed with neighbor-joining method. Results The 23 necrophagous Calliphorid flies were identified to 9 species of 5 genera. The 715 bp from 28S rRNA and 637 bp from COⅠ gene were obtained and the online BLAST result showed more than 99% of similarity. The phylogeny tree showed that the necrophagous flies could cluster well into 9 groups, which was consistent with morphological identification results. The intraspecific difference in 28S rRNA was 0 and the interspecific difference was 0.001-0.033. The intraspecific difference in COⅠ was 0-0.008 and the interspecific difference was 0.006-0.101. Conclusion Combined use of 28S rRNA and COⅠ gene sequence fragments can effectively identify the nine Calliphorid flies in this study. However, for closely related blowfly species, more genetic markers should be explored and used in combination in future.
Animals ; DNA, Mitochondrial/genetics* ; Diptera/genetics* ; Phylogeny ; RNA, Ribosomal, 28S/genetics* ; Sequence Analysis, DNA ; Species Specificity

Objective To explore the CT manifestations of primitive neuroectodermal tumor (PNET) of adrenal gland,aiming to increase the cognition on this disease.Methods The CT manifestations of 7 patients who were pathologically diagnosed with adrenal gland PNET were analyzed retrospectively.Results The age of patients was 24-63 years old,with average age of (47.6±13.7) years,including 6 females and 1 male.Location of PNET:4 in left adrenal gland and 3 in right adrenal gland.Clinical manifestations:3 cases had upper abdominal distension,2 cases suffered from pain of waist and back,1 case was discovered in physical examination and another 1 had fever.No abnormality was found in laboratory and endocrinological examinations.After operation,4 cases had recurrence and 2 had distant metastasis.During follow-up,6 patients died and only 1 still alive.CT showed that the tumor,whose maximum diameter was 10.1-19.4 cm,was elliptic or lobulated in shape.The tumor was clear in boundary in 2 patients,but was unclear in boundary and involved adjacent organs in 5 patients.The plain scanning showed equidensity or slightly low density,complicated with necrosis and cystic lesions without calcification.The enhanced scanning suggested progressive uneven enhancement,with multiple interatrial septum-like changes and latticed enhancement inside.Conclusion CT manifestations of adrenal gland PNET can prompt the diagnosis,pathological examination is still required for confirmation.CT can accurately describe the internal structures,adjacent relationship and the metastasis of tumors.