Efficacy and safety of different Janus kinase inhibitors combined with methotrexate for the treatment of rheumatoid arthritis: a single-center randomized trial

Abstract Objective To compare the efficacy and safety between baricitinib (BARI) and tofacitinib (TOFA) for the treatment of the rheumatoid arthritis (RA) patients receiving methotrexate (MTX) in clinical practice. Methods This retrospective study recruited 179 RA patients treated with BARI (2-4 mg/d) or TOFA (10 mg/d) at The First Affiliated Hospital of Guangxi Medical University from September 2019 to January 2022. The rate of low disease activity (LDA) was used as the primary end point. Secondary end points included the Disease Activity Scale-28 (DAS-28)-C-reactive protein (CRP); the rate of DAS28-CRP remission; visual analogue scale (VAS) for pain, swollen joint, and tender joint counts; and adverse events at the 6-month follow-up. Several factors affecting LDA achievement were also analyzed. Results Seventy-four patients were treated with BARI and 105 were treated with TOFA, including 83.24% females, with a median (IQR) age of 56.0 (53.0-56.0) years old and disease duration of 12.0 (6.0-12.0) months. There was no difference of the rate of LDA between the BARI and TOFA treatment groups. All disease indices in the two groups were significantly improved, including a significantly lower VAS in the BARI group (P < 0.05), reflecting the drug efficacy after 1 and 6 months of treatment. The incidence of adverse reactions was similar in these two groups. Conclusion The treatment efficacy and safety of BARI and TOFA in the RA patients were similar, but BARI was more effective in pain relief than TOFA. An older baseline age was more likely to achieve LDA in the BARI group, while a low baseline erythrocyte sedimentation rate (ESR) was more likely to achieve LDA in the TOFA group.

Protection of Schisandra chinensis extract in paraquat-induced pulmonary fibrosis in mice / 天津医药

Objective To explore the protective effcets of Schisandra chinensis extract (SCE) in paraquat (PQ)-induced pulmonary fibrosis in mice ,and its intrinsic molecular mechanisms thereof. Methods A total of 108 mice were randomly allocated into six groups (n=18):control group, model group, low concentration of SCE group (200 mg/kg), medium concentration of SCE group (400 mg/kg), high concentration of SCE group (800 mg/kg) and vitamin C group (100 mg/kg). Except control group, mice were given by intragastric administration with PQ (100 mg/kg) and administered with SCE and Vitamin C once per 24 h after PQ modeling. Mice were sacrificed at 7, 14 and 21 d after modeling. Six mice were executed at different time points. The degree of lung tissue inflammation and fibrosis were observed by HE staining and Masson staining. The mRNA and protein expression levels of transforming growth (TGF)-β1, interleukin (IL)-6 and IL-17 in lung tissue were determined by RT-PCR and ELISA respectively. Results (1) Compared with control group, the lung tissue of model group showed a large number of inflammatory cell infiltration, space congestion, and its inflammation scores increased at 7 and 14 days after modeling (P<0.05). At the same time, compared with model group and vitamin C group, inflammation scores were significantly decreased in medium concentration of SCE group and high concentration of SCE group (P<0.05). (2) Compared with control group, collagen fibers and the degree of fibrosis were significantly increased in model group ,while pulmonary fibrosis were decreased in medium concentration of SCE group and high concentration of SCE group at 14 and 21 days after modeling (P<0.05). (3) With the extension of modeling time, both mRNA and protein expressions of TGF-β1 were obviously elevated, IL-6 decreased and IL-17 reduced after the first increase in PQ group. Compared with PQ group, levels of three cytokines mRNA and protein expression in medium concentration of SCE group and high concentration of SCE group changed as follows:IL-6 level was markedly decreased at 7 and 14 days after modeling;TGF-β1 level was markedly increased at 14 and 21 days after modeling. However, IL-17 level was markedly decrease at three time points(P<0.05). Conclusion SCE can relieve PQ-induced lung inflammation and fibrosis by suppressing TGF-β1, IL-6, and IL-17 expressions.

Expression and prognostic value of regulatory T cells and M2 macrophages in diffuse large B-cell lymphoma tissues / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the prognostic value of regulatory T cells (Tregs) and M2 macrophages in diffuse large B-cell lymphoma (DLBCL) tissues.</p><p><b>METHODS</b>The expression of CD163 and Foxp3 was detected by immunohistochemistry in 92 cases of DLBCL, and it was statistically analyzed whether their expressions correlate with clinical data and prognosis in patients with DLBCL.</p><p><b>RESULTS</b>The density of M2 macrophage and regulatory T cells in DLBCL tumor tissues was significantly higher than that in the adjacent tissues (P = 0.02, P = 0.04). The expression of M2 macrophages was significantly positively correlated with regulatory T cells expression (r = 2.012, P < 0.05). High density of M2 or Tregs had a relationship with extranodal involvement (P < 0.05). Cox regression analysis showed that the expressions of CD163 and Foxp3 were independent prognostic factors of DLBCL (P < 0.05).</p><p><b>CONCLUSIONS</b>Combined detection of the expression of CD163 and Foxp3 proteins and then evaluation of the amount of M2 macrophages and Tregs can be used to more closely predict the prognosis for DLBCL patients.</p>

Evaluation of biological safety of silicon membrane embedded permanent magnets implanted in canine / 第二军医大学学报

Objective To investigate the biological safety of silicon membrane embedded permanent magnets implanted into canine, so as to evaluate the safety of a micturition alert device designed on the principle of compass. Methods Twelve adult male dogs (weighing 11-12 kg) were divided into experimental group (8 dogs) and control group (4 dogs ). The experimental group was implanted with a silicon membrane embedded NdFeB magnet, which was 10 mm in diameter and 3 mm in thickness and with a magnetic induction intensity of 0. 3 Tesla at the center of the pole face surface. The control group was implanted with a silicon membrane embedded NdFeB alloy with the same dimensions. The grafts were sutured onto the anterior surface of the bladder wall. The dogs were then allowed to live for one year. Both the survival and local pathology around the grafts were observed after implantation. And the pre-operation urine and post-operation urine were compared between the two groups. Results One dog in the experimental group died from operation complications 10 hours after operation, another dog had intestinal obstruction 3 weeks after operation because iron wires in the intestinal tract was caught up by the permanent magnet. The rest 6 dogs in the experimental group and 4 dogs in the control group had no abnormalities in spirit, appetite, urine or stool, and there were no infections. The animals were sacrificed one year after operation. Adhension was found between the epiploon and the bladder wall around permanent magnets in these 10 dogs; the fibrous capsule around the permanent magnets was thin, and the local bladder wall below permanent magnets was thickened, with normal bladder mucosa. Grade 2 inflammatory reaction and fibrous capsule of the local tissue were noted around the grafts. The findings of urine routine were normal before and after operation. Conclusion NdFeB permanent magnets embedded with silicon membrane are biologically safe for clinical application, which warrante further investigations.

Expression and significance of human beta-defensin in recurrent nasal polyps / 中南大学学报(医学版)

OBJECTIVE@#To observe the expression of human beta-defensin-1 (hBD-1) and human beta-defensin-2 (hBD-2) in recurrent nasal polyps, and to investigate the role of beta-defensin in the recurrent nasal polyps.@*METHODS@#Tissues of nasal polyps was obtained from 10 patients with nasal polyps undergoing endoscopic sinus surgery, recurrent nasal polyps from 10 patients 6 months after surgery, nasal mucosa from 10 recovered patients with nasal polyps postoperatively and,10 control subjects. hBD-1 mRNA and hBD-2 mRNA levels of tissue specimens in all groups were detected by reverse transcriptase-polymerase chain reaction (RT-PCR).@*RESULTS@#There was no significant difference in hBD-1 mRNA level between the 4 groups (P>0.05). Expression of hBD-2 mRNA was detected in patients with nasal polyps and recurrent nasal polyps, but rare in the recovered patients and the control subjects.@*CONCLUSION@#hBD-1 is a constitutive expression and hBD-2 is an induced expression. beta-Defensin may play an important role in forming the nasal polyps.

Clinical observations of the effects on the lower limb function after lumbar or sacral nerve root transferring to reconstruct urination function / 中华外科杂志

<p><b>OBJECTIVE</b>To observe the effects on the lower limbs function after lumbar or sacral nerve root transferring to reconstruct urination function.</p><p><b>METHODS</b>Nine patients with bladder dysfunction and normal lower limb function after spinal cord injury were treated with anastomosis the S2 or S3 nerve root with the normal lumbar or sacral nerve root to reconstruct a new bladder artificial reflex arc. Then the alterations on the sensation and motor function of the lower limb after the surgery were observed.</p><p><b>RESULTS</b>Myodynamia of the legs decreased slightly, and the decreasing about half grade of the myodynamia in the plantar flexion of the ankles were detected in 4 of 9 patients with S1 transferring. And the myodynamia recovered 3 months postoperatively. No obvious decreasing of the myodynamia appeared in the other cases.</p><p><b>CONCLUSION</b>No obvious effects on the motor function can be found after the single lumbar or sacral nerve root transferring to reconstruct urination function.</p>

Liposomal honokiol, a potent anti-angiogenesis agent, in combination with radiotherapy produces a synergistic antitumor efficacy without increasing toxicity

Honokiol is an active compound purified from magnolia that has been shown to induce cell differentiation, apoptosis, and anti-angiogenesis effects, as well as an enhancement in tumor growth delay in combination with chemotherapeutic agents in several mouse xenograft models. Our goal was to investigate the radiosensitization effect of honokiol on lung carcinoma. The radiosensitization effect of liposomal honokiol in Lewis lung carcinoma cells (LL/2) was analyzed using an in vitro clonogenic survival assay. For an in vivo study, Lewis lung carcinoma-bearing C57BL/6 mice were treated with either liposomal honokiol at 25 mg/kg or 5 Gy of single tumor radiation, or a combination of both over 12 days of treatment. The tumor growth delay and the survival time were evaluated. In addition, histological analysis of tumor sections was performed to examine changes by detecting the microvessel density and apoptosis in tumor tissues. In the clonogenic survival assay, LL/2 cells treated with IC50 Lipo-HNK for 24 h showed a radiation enhancement ratio of 1.9. After 12 days of combination treatment, the tumor volume decreased 78% and produced an anti-tumor activity 1.3-fold greater than a predicted additive effect of honokiol and radiation alone. This combination treatment also caused an 8.7 day delay in tumor growth. The cell cycle distribution and histological analysis demonstrated that liposomal honokiol has an anti-tumor effect via inducing apoptosis and inhibiting angiogenesis. Liposomal honokiol can enhance tumor cell radiosensitivity in vitro and in vivo, indicating that radiotherapy combined with liposomal honokiol can lead to greater anti-tumor efficacy.

Effects of nitrogen fertilization strategies on nitrogen use efficiency in physiology, recovery, and agronomy and redistribution of dry matter accumulation and nitrogen accumulation in two typical rice cultivars in Zhejiang, China / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Field experiments were conducted in farmers' rice fields in 2001 and 2002 to study the effects of nitrogen (N) management strategies on N use efficiency in recovery (RE), agronomy (AE) and physiology (PE) and redistribution of dry matter accumulation (DMA) and nitrogen accumulation (NA) in two typical rice cultivars in Jinhua, Zhejiang Province. This study aimed mainly at identifying the possible causes of poor fertilizer N use efficiency (NUE) of rice in Zhejiang by comparing farmers' fertilizer practice (FFP) with advanced site-specific nutrient management (SSNM) and real-time N management (RTNM). The results showed that compared to FFP, SSNM and RTNM reduced DMA and NA before panicle initiation and increased DMA and NA at post-flowering. There is no significant difference between SSNM and FFP in post-flowering dry matter redistribution (post-DMR) and post-flowering nitrogen redistribution (post-NR). These results suggest that high input rate of fertilizer N and improper fertilizer N timing are the main factors causing low NUE of irrigated rice in the farmer's routine practice of Zhejiang. With SSNM, about 15% of the current total N input in direct-seeding early rice and 45% in single rice could be reduced without yield loss in Zhejiang, China.

Potential production simulation and optimal nutrient management of two hybrid rice varieties in Jinhua, Zhejiang Province, China / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Potential growth of two widely-grown hybrid rice varieties in the Jinhua district of Zhejiang Province, Shanyou63 for mid-rice and Xieyou46 for late rice, was simulated using a crop growth model of WOFOST. Parameters of the rice growth in WOFOST were calibrated through field experiments from 1999 to 2002 in Jinhua. The potential yield simulated with WOFOST was about 12 t/ha for Shanyou63 and 10 t/ha for Xieyou46, which are in good agreement with the highest recorded yield obtained in this area. Under farmers practice, current yield is about 7.5 t/ha for Shanyou63 and 6.5 t/ha for Xieyou46. There is a gap between the actual rice yield and the potential yield for these two hybrid rice varieties grown in this area. The attainable target yields were set to 70% to 75% of their potential yields for the two varieties. A recently developed software "Nutrient Decision Support System (NuDSS)" for irrigated rice was used to optimize nutrient management for these two rice varieties. According to NuDSS, the optimal fertilizer N requirement for the target yields was about 150 kg/ha for Shanyou63 and about 120 kg/ha for Xieyou46, which were only about 70% of the fertilizer N application under current farmers' practice. Comparing with farmers' practice, there is great potential to increase actual rice yields and to reduce fertilizer N use rates by improving rice crop management practice in Jinhua.

Establishment of 2-dimensional gel electrophoresis map and analysis of proteomics from human nasal polyps / 中南大学学报(医学版)

OBJECTIVE@#To establish 2-dimensional polyacrylamide gel electrophoresis (2-DE) map from human nasal polyps and normal nasal mucosa, and to identify differential expression proteins of 2-DE map.@*METHODS@#Samples of nasal polyps and nasal mucosa (each sample group containing 7 cases) were obtained. The total proteins were extracted and separated by immobilized pH gradient (IPG)-based 2-DE. The silver-stained 2-DE was scanned with digital Imagescanner and analyzed with ImageMaster 2-DE Elite 4.01 software. To obtain peptide mass fingerprint (PMF) of differential protein spots, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was used. The PMF was searched in Swiss-Prot and TreMBL database by Pept-Ident software, to identify differential expression proteins.@*RESULTS@#The well-resolved, reproducible 2-DE maps of nasal polyps and nasal mucosa were established. For the polyps tissues, the average proteins spot of three 2-DE maps was 825+/-78; and 682+/-96 spot was matched with the average matching rate of 82.7%. The average deviations of matched spot position were (1.13+/-0.16) mm in IEF direction and (1.45+/-0.21) mm in SDS-PAGE direction, respectively. For the nasal mucosa tissues, the average proteins spot of three 2-DE maps was 936+/-62; and 821+/-78 spots were matched with the average matching rate of 87.7%. After comparing the 2-DE maps of nasal polyps and nasal mucosa tissues, the protein spots were 1,458 and 1,617 respectively; and 1,026 protein spots were matched. Forty differential expression protein spots were incised from silver staining gel randomly and digested in the gel by TPCK-Trypsin. Thirty-four PMFs were obtained by MALDI-TOF-MS and 24 differential proteins were identified.@*CONCLUSION@#The well-resolved, reproducible 2-DE maps of human nasal polyps and nasal mucosa have been successfully established. Certain differential proteins related to the pathogenesis of human nasal polyps are identified.

Dynamic changes of adrenocorticotropic hormone (ACTH) and cortisol (Cr) in SARS patients who received large dose of methylprednisolone therapy / 中国实用内科杂志

8 000 mg group was lower than the normal control's(P

Studies on nutrient uptake of rice and characteristics of soil microorganisms in a long-term fertilization experiments for irrigated rice / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The ecosystem characteristics of soil microorganism and the nutrient uptake of irrigated rice were investigated in a split-block experiment with different fertilization treatments, including control (no fertilizer application), PK, NK, NP, NPK fertilization, in the main block, and conventional rice and hybrid rice comparison, in the sub block. Average data of five treatments in five years indicated that the indigenous N supply (INS) capacity ranged from 32.72 to 93.21 kg/ha; that indigenous P supply (IPS) capacity ranged from 7.42 to 32.25 kg/ha; and that indigenous K supply (IKS) capacity ranged from 16.24 to 140.51 kg/ha, which showed that soil available nutrient pool depletion might occur very fast and that P, K deficiency has become a constraint to increasing yields of consecutive crops grown without fertilizer application. It was found that soil nutrient deficiency and unbalanced fertilization to rice crop had negative effect on the diversity of the microbial community and total microbial biomass in the soil. The long-term fertilizer experiment (LTFE) also showed that balanced application of N, P and K promoted microbial biomass growth and improvement of community composition. Unbalanced fertilization reduced microbial N and increased C/N ratio of the microbial biomass. Compared with inbred rice, hybrid rice behavior is characterized by physiological advantage in nutrient uptake and lower internal K use efficiency.

Identification of technology options for reducing nitrogen pollution in cropping systems of Pujiang / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

This work analyses the potential role of nitrogen pollution technology of crop systems of Pujiang, County in Eastern China's Zhejiang Province, rice and vegetables are important cropping systems. We used a case study approach involving comparison of farmer practices and improved technologies. This approach allows assessing the impact of technology on pollution, is forward looking, and can yield information on the potential of on-the-shelf technology and provide opportunities for technology development. The approach particularly suits newly developed rice technologies with large potential of reducing nitrogen pollution and for future rice and vegetables technologies. The results showed that substantial reductions in nitrogen pollution are feasible for both types of crops.

Relationship between RAR-? gene expression defect and its methylation / 中华妇产科杂志

Objective To evaluate the expression of RAR-? gene in cervical carcinoma cell lines SiHa,HeLa,C33A and Caski and to analyze the relation between their gene expression and the promoter methylation of RAR-? DNA.Methods The expression of mRNA and protein of RAR-? gene in the four cell lines were analyzed by RT-PCR,western blot and immunofluoreseence,respectively.Methylation specific PCR(MSP)was used to check whether there was methylation in the promoter of RAR-? gene.The demethylating agent 5-aza-2'-deoxycytidine(5-Aza-cdR)was used to treat methylated cell lines and the change of RAR-? gene methylation and RAR-? gene expression defects were observed.The cell proliferation was assayed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.Results The mRNA and protein expression levels of RAR-? in cell lines SiHa,HeLa,Caski and C33A were 0.25 ?0.08,0,0.60?0.19,3.12?0.92 and 0.23?0.07,0,0.14?0.05,0.68?0.21,respectively.The mRNA and protein expression of RAR-? in SiHa,HeLa and Caski cell lines were decreased or silenced, whereas its expression increased in C33A cell line.MSP method showed that there were RAR-? gene methylation in SiHa,HeLa and Caski cell lines,while there was no RAR-? gene methylation in C33A cell line.After treated with 5-Aza-cdR,the mRNA and protein expression levels of RAR-? in SiHa,HeLa, Caski and C33A cell lines were 1.82?0.59,2.13?0.62,1.67?0.43,2.95?0.89 and 0.69?0.21, 0.83?0.29,0.56?0.16,0.64?0.20 respectively.The mRNA and protein levels of RAR-? had a significant difference between before and after interference with 5-Aza-cdR in SiHa,Helm,and Caski cell lines(P0.05).The 5-Aza-cdR treatment could suppress cell proliferation.Conclusions The RAR-? gene expression defects play an important role in the carcinogenesis of cervical cancer.Aberrant methylation in promotor region of RAR-? gene may be an important mechanism for the loss of expression of RAR-? gene.