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.

Ferroptosis-induced effect and mechanism of dihydroartemisinin on tumor cells / 中草药

Objective: To explore the effect and mechanism of dihydroartemisinin (DHA) in inducing ferroptosis of tumor cells. Methods: 3,3',5,5'-Tetramethylbenzidine was used to detect the oxygen free radicals (•OH) formed by DHA and FeSO4 in vitro. The cytotoxicity of DHA on HepG2 cells was detected by MTT method (including FeSO4 or deferoxamine pretreated groups). MTT assay was used to investigate the influence of glutathione (GSH) and inhibitor (Fer-1) on cytotoxicity of DHA; DCFH-DA dye was used to investigate intracellular reactive oxygen species induced by DHA (including FeSO4 pretreated groups). C11-BODIPY581/591 and DiO dye were used to examine the influence of DHA (including FeSO4 pretreated groups) on intracellular lipid peroxide formation and cell membrane structure; Glutathione peroxidase assay kit was used to explore the influence of DHA (including FeSO4 pretreated groups) on intracellular activity GPX-4 in HepG2 cells. Results: Fenton-like reaction occurred between DHA and Fe2+, and •OH was produced during the reaction. The half-inhibitory concentration (IC50) of DHA was (39.96 ± 8.78) μmol/L. FeSO4 and deferoxamine could increase or decrease the cytotoxicity of DHA, respectively. After treated with DHA, the intracellular content of reactive oxygen species and lipid peroxide was increased, the cell morphology became larger, and the cell membrane was broken. Compared with the DHA treated group, the FeSO4 pretreated group further increased the intracellular reactive oxygen species and lipid peroxide content, and the cell membrane morphology was completely destroyed. FeSO4 could also enhance the inhibitory effect of DHA on GPX-4 activity. Conclusion: DHA increases intracellular reactive oxygen species through Fenton-like reaction and ultimately induces ferroptosis of tumor cells. In addition, exogenous iron can accelerate the Fenton-like reaction of DHA and accelerate the occurrence and development of ferroptosis of tumor cells.

Impact of LDB3 gene polymorphisms on clinical presentation and implantable cardioverter defibrillator (ICD) implantation in Chinese patients with idiopathic dilated cardiomyopathy / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Objective: Mutations in LIM domain binding 3 (LDB3) gene cause idiopathic dilated cardiomyopathy (IDCM), a structural heart disease with a complicated genetic background. However, the association of polymorphisms in the LDB3 gene with susceptibility to IDCM in Chinese populations remains unexplored as dose the impact on clinical presentation. Methods: We sequenced all exons and the adjacent part of introns of the LDB3 gene in 159 Chinese Han IDCM patients and 247 healthy controls. Then we detected the distribution of polymorphisms in the LDB3 gene in all participants and assessed their associations with risk of IDCM. Additionally, we conducted a stratified genotypephenotype correlation analysis. Results: The A allele of rs4468255 was significantly associated with IDCM (P<0.01). The rs4468255, rs11812601, rs56165849, and rs3740346 were also associated with diastolic blood pressure (DBP) and left ventricular ejection fraction (LVEF) (P<0.05). Notably, a higher frequency of rs4468255 polymorphism was observed in implantable cardioverter defibrillator (ICD) recipients under a recessive model (P<0.01), whereas the significant association disappeared after adjusting for potential confounders. However, in the dominant model, notable correlations could only be observed after adjusting for multi parameters. Conclusions: The rs4468255 was significantly correlated with IDCM of Chinese Han population. A allele of rs4468255 is higher in IDCM patients with ICD implantation, suggesting the influence of genetic background in the generation of this response. In addition, rs11812601, rs56165849, and rs3740346 in LDB3 show association with brain natriuretic peptide, DBP, and LVEF levels in patients with IDCM but did not show any association with IDCM susceptibility.

Advance in research of biodegradable mesoporous silica nanoparticles / 药学学报

Mesoporous silica nanoparticles (MSNs) have been widely used as drug carriers in the diagnosis and treatment of diseases due to their specific characteristics, which include a large surface area, ordered mesoporous structures, easy surface modification and feasible sustained release action for encapsulated drugs. With the research development of MSNs, the biodegradability and removability of mesoporous silica nanomaterials have attracted considerable attention in the clinical application of the MSNs-based formulations. This paper was prepared to emphasize the preparation approaches of biodegradable mesoporous silica nanoparticles through the metal oxide doping method and the organic compound doping method. We discussed the biodegradable mechanism and process of such nanoparticles, and finally, provided an insightful and helpful review of the prospective application of the biodegradable mesoporous silica nanoparticles in medical field.

The effect of low molecular weight heparin in the treatment of patients with intrahepatic cholestasis pregnancy ;and regulation of cytokines / 中国基层医药

Objective To observe the effect of low molecular weight heparin in the treatment of patients with intrahepatic cholestasis pregnancy(ICP)and regulation of cytokines.Methods 124 patients with ICP were randomly divided into observation group and control group.The control group was treated with SAMe +UDCA therapy,the con-trol group was added low molecular weight heparin.All patients were treated for 10 days.Alanine aminotransferase (ALT),aspartate aminotransferase (AST),total bile acid (TBA),tumor necrosis factor alpha (TNF -α)and IL-18 were observed before and after treatment.Results After treatment,ALT,AST and TBA levels were lower in the two groups(t=64.48,110.14,45.75,40.76,62.54,24.67,all P=0.000),which of the observation group were higher(t=62.42,49.42,23.03,all P=0.000).After treatment,the TNF-αand IL-18 levels were lower in the two groups(t=13.14,25.07,all P=0.000),the TNF-αlevel in the observation group was lower than the control group(t=4.91,P=0.000).After treatment,the incidence rates of neonatal meconium,neonatal asphyxia of the observation group were significantly lower than those of the control group(7.14%vs.20.69%,χ2 =4.33,P=0.037;8.93% vs.24.14%,χ2 =4.75,P=0.029).The incidence rate of fetal and maternal hemorrhage between the two groups had no statistically significant differences (1.79% vs.1.72%,χ2 =0.00,P=0.980;5.17% vs.3.57%,χ2 =0.17,P=0.680).Conclusion The effect of low molecular weight heparin in the treatment of patients with intrahepatic cholestasis of pregnancy is exact,it can reduce the biochemical markers and inflammatory cytokine expression and improve perinatal outcome,which deserves to promote in the clinical treatment application.

Clinical observation of needle revision and 5-fluorouracil subconjunctive injection for the dysfunctional filtering blebs / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the efficacy and safety of needle revision with 5-fluorouracil (5-FU) on the dysfunctional filtering blebs after trabeculectomy and to assess the factors that may impact the success. METHODS:Eighty- three eyes in 76 patients underwent the needle revision and 5-FU subconjunctive injection for the dysfunctional blebs after trabeculectomy and were followed up for 12mo. The intraocular pressure ( IOP), the number of drugs, corneal endothclium, bleb morphology and complications were observed and recorded. RESULTS: IOP decreased significantly from 35. 3 ±5. 8mmHg(1kPa = 7. 5mmHg) of pre - needling to 17. 0 ±4. 3mmHg of post - needling ( P CONCLUSION: The needle revision combined with 5-FU is a safe, effective and simple method. Dysfunctional blebs should be treated early after trabeculectomy.

Preparation and in vitro evaluation of borneol and folic acid co-modified doxorubicin loaded PAMAM drug delivery system / 药学学报

A novel targeting drug carrier (FA-BO-PAMAM) based on the PAMAM G5 dendrimer modified with borneol (BO) and folic acid (FA) molecules on the periphery and doxorubicin (DOX) loaded in the interior was designed and prepared to achieve the purposes of enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. 1H NMR was used to confirm the synthesis of FA-BO-PAMAM; its morphology and mean size were analyzed by dynamic light scattering (DLS) and transmission electron microscope (TEM). Based on the HBMEC and C6 cells, cytotoxicity assay, transport across the BBB, cellular uptake and anti-tumor activity in vitro were investigated to evaluate the properties of nanocarriers in vitro. The results showed that the nanocarrier of FA-BO-PAMAM was successfully synthesized, which was spherical in morphology with the average size of (22.28 ± 0.42) nm, and zeta potential of (7.6 ± 0.89) mV. Cytotoxicity and transport across the BBB assay showed that BO-modified conjugates decreased the cytotoxicity of PAMAM against both HBMEC and C6 cells and exhibited higher BBB transportation ability than BO-unmodified conjugates; moreover, modification with FA increased the total uptake of DOX by C6 cells and enhanced the cytotoxicity of DOX-polymer against C6 cells. Therefore, FA-BO-PAMAM is a promising nanodrug delivery system in employing PAMAM as a drug carrier and treatment for brain glioma.

Immunophenotypic comparison of adipose-derived mesenchymal stem cells from the greater omentums and subcutaneous adipose tissues of rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the adipose-derived mesenchymal stem cells (ADMSCs) isolated from the greater omentums and subcutaneous adipose tissues of rats for their characteristics in cell morphology, growth kinetics and immunophenotypes.</p><p><b>METHODS</b>ADMSCs were isolated from the greater omentums and inguinal fat pads of 6 SD rats and cultured in vitro. The morphologies of the ADMSCs were observed using phase-contrast microscopy, and their growth curves were generated and the doubling times determined. The phenotypic marker profiles including CD11b, CD29, CD45, CD49d, CD90 and CD106 of the ADMSCs in the fourth passage were determined using flow cytometry.</p><p><b>RESULTS</b>The ADMSCs harvested from the greater omentums and inguinal fat pads showed almost identical morphologies. The growth curves and the mean doubling time of the ADMSCs from the two different sources showed no obvious difference. With similar positivity rates for CD11b, CD29, CD106 and CD90, the two ADMSCs exhibited different expression rates of CD45 and CD49d.</p><p><b>CONCLUSIONS</b>The immunophenotypic characteristics of the ADMSCs from the greater omentums and subcutaneous adipose tissues are not totally identical.</p>

Spermatic vein and artery ligation for varicocele / 中华男科学杂志

<p><b>OBJECTIVE</b>To assess the influence of spermatic vein and artery ligation on testicular hemodynamics, spermatogenesis and testis volume in varicocele patients.</p><p><b>METHODS</b>Eighty-eight varicocele patients were randomly divided into a spermatic vein and artery ligation (n = 46) and a spermatic vein and artery preservation group (n = 42). The testicular hemodynamic parameters, testis volume and results of semen analyses were obtained before and 6 months after the surgery and compared between the two groups.</p><p><b>RESULTS</b>There were no significant differences in peak systolic velocity (V(max)), end diastolic velocity (V(min)), mean enveloped velocity (V(mean)) and V(min) of the capsular artery (CA) either between the ligation and preservation groups (P > 0.05) or between pre- and post-operation (P > 0.05). Sperm density, vitality and motility were significantly improved after surgery (P < 0.01), with no significant differences between the two groups (P > 0.05). No significant difference was found in the testis volume between the two groups before and after the operation (P > 0.05).</p><p><b>CONCLUSION</b>Spermatic vein and artery ligation in varicocelectomy does not affect the testicular hemodynamics, spermatogenesis and testis volume of varicocele patients. Both the spermatic vein and artery should be ligated when necessary.</p>

Epidemiological Analysis of Traffic Deaths in Xiaoshan District from 2002 to 2007 / 预防医学

Objective To analyze the epidemiological characteristics of traffic deaths in Xiaoshan district which provides evidence for the prevention and control of traffic accidents. Methods Basing on the data obtained from death surveillance system of Xiaoshan from 2002 to 2007, ICD-10 was used to classify death causes. The mortality and proportion of death causes of traffic accident were calculated. Results The mortality of traffic accident was 26.28/100, 000, which ranked the first among all death causes of injury. The mortality in male was significantly higher than that in female, and increased with age. Death resulted from the vehicle-man collision was on the top among the 9 kinds of deaths due to traffic accidents, and 46.43% of death were the people over 60 years old. Motorcycle accident incidence was common in the age of 20 to 59 years old, accounting for 91.80% of motorcycle deaths, in which male was the major victims, accounting for 87.12%. Conclusion Traffic accidents have become an important public health issue in Xiaoshan District. Social departments should actively take measures to strengthen the propaganda and education of road traffic laws and regulatiens to reduce traffic accidents and deaths.

Effect of mica monomer powder on chief and parietal cells as well as G and D cells in gastric mucosa of chronic atrophic gastritis in rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the regulative action of mica monomer powder preparation on the chief and parietal cells as well as G and D cells in the gastric mucosa of the experimental atrophic gastritis (CAG) rats.</p><p><b>METHODS</b>Intervention therapy was given to the experimental CAG rats at three different doses of mica monomer powder preparation to evaluate the changes of chief and parietal cells as well as G and D cells in the gastric mucosa and the histopathological changes of gastric mucosa.</p><p><b>RESULTS</b>Mica monomer powder preparation at three different doses could increase the amount of chief and parietal cells as well as G and D cells in gastric mucosa of the experimental CAG rats and alleviate and control the inflammation of gastric mucosa and the atrophy of gastric mucosa glands. Especially, better effects were shown in the mid and high dose groups.</p><p><b>CONCLUSION</b>Mica has the pharmacological action of protecting the gastric mucosa, enhancing blood flow of the gastric mucosa, and consequently improving the inflammatory responses of the gastric mucosa. One of the mechanisms is associated with promoting the secretion of gastric acid and gastric pepsin and regulating the neuroendocrine mechanism including gut hormone secretion (gastrin and somatostatin) by increasing the number of chief and parietal cells as well as G and D cells.</p>

Effect of mica granule on the expression of gene-protein associated with cancer in gastric mucosa tissue of chronic atrophic gastritis rats / 中国中药杂志

<p><b>OBJECTIVE</b>To research the regulative effect of mica monomer granule preparation on the expression of gene associated with cancer in gastric mucosa tissue of experimental chronic atrophic gastritis (CAG) rats.</p><p><b>METHOD</b>To treat experimental CAG rats using mica monomer granule preparation with three different dosage-high, moderate and low level respectively. To observe the expression changes of mutant antioncogene-p53 gene-protein, oncogene p21, antioncogene p16 and anti-apoptosis gene bcl-2 in gastric mucosa of CAG rats by two-step ways of EnVision system in immunohistochemical method.</p><p><b>RESULT</b>There was the tendency that mica monomer granule preparation with three different dosage could decrease the expression of p53 as well as p21, and mica had the obvious regulative effects on deletion of p16 and high-expression of bcl-2. It could also alleviate the inflammation of gastric mucosa and promote the regeneration of gland.</p><p><b>CONCLUSION</b>The treatment and reversion action of mica on chronic atrophic gastritis is probably related with the regulative effect on the expression of gene associated with cancer.</p>

Effect of mica monomer granule on gastrin, somatostatin and G cells as well as D cells of gastric mucosa in CAG rat / 中国中药杂志

<p><b>OBJECTIVE</b>To study regulative action of mica monomer granule preparation on gastrin (GAS), somatostatin (SS) and G cells as well as D cells of gastric mucosa in experimental chronic atrophic gastritis (CAG) rat.</p><p><b>METHOD</b>CAG rats were treated with mica monomer granule preparation with three different dosages--high, moderate and low level respectively. Changes of blood serum GAS, blood plasma SS and G cells as well as D cells of gastric mucosa in CAG rats were observed and detected with ELISA method, RIA method and immunocytochemistry method.</p><p><b>RESULT</b>Mica monomer granule of three different dosages could increase the quantity of G cells as well as D cells of gastric mucosa and the concentration of blood serum GAS and decrease the content of blood plasma SS in CAG rat at different level respectively. It was more effective in high and moderate dosage groups.</p><p><b>CONCLUSION</b>Mica has the pharmacological action of protecting gastric mucosa, promoting the palingenesis of gastric gland and enhancing blood stream of gastric mucosa consequently to abate the inflammation reaction of gastric mucosa. Its effective mechanism is associated with the neuroendocrine regulative mechanism of promoting the secretion of gastric acid and gastric pepsin by increasing the amount of G cells as well as D cells and the concentration of blood serum GAS, and reducing inhibiting action on GAS secretion and enhancing the secretion of GAS by decreasing the content of SS.</p>

An experimental study(II) on the inhibition of prostatic hyperplasia by extract of seeds of Brassica alba / 中国中药杂志

<p><b>OBJECTIVE</b>To study the active components and their functionary mechanism of the extract of Brassica alba seeds, which inhibits experimental mice prostatic hyperplasia.</p><p><b>METHOD</b>Prostatic hyperplasia of castrated male mice induced by testosterone propionate, the penetrability of capillary vessel of mice skin induced by histamine and the endermic flesh bud of rat induced by filter paper were used as experimental models. Sinalbin and beta-sitosterol separated from seeds of Brassica alba were used to test the activities.</p><p><b>RESULT</b>Sinalbin and beta-sitosterol(16.0 mg.kg-1.d-1 and 8.0 mg.kg-1.d-1) could significantly inhibit mice prostatic hyperplasia induced by testosterone propionate and activity of serum acid phosphatase(P < 0.01 or P < 0.05), Sinalbin(16.0 mg.kg-1.d-1)could significantly inhibit the hyperplasia of endermic flesh bud in rat induced by filter paper(P < 0.05), beta-sitosterol(16.0 mg.kg-1.d-1 and 8.0 mg.kg-1.d-1) could significantly decrease the penetrability of capillary vessel of mice skin induced by histamine.</p><p><b>CONCLUSION</b>Sinalbin and beta-sitosterol have anti-androgen and anti-inflammation activities.</p>

An experimental study(I) on the inhibition of prostatic hyperplasia with extract of seeds of Brassica alba / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effective fraction of the extract of seeds of Brassica alba, which inhibits experimental mice prostatic hyperplasia.</p><p><b>METHOD</b>An experimental model of prostatic hyperplasia of castrated male mice induced by testosterone propionate was made. Fractions I, II and III were prepared by extracting the seeds of Brassica alba successively with ether, ethanol and water under reflux. Total extract was prepared by extracting the seeds of Brassica alba with 60% ethanol under reflux. The total extract and the three fractions were used to test the activities.</p><p><b>RESULT</b>Total extract, fractions I and II could not only significantly inhibit mice prostatic hyperplasia induced by testosterone propionate and activity of serum acid phosphatase, but also decrease wet weight of preputial glands, while fraction III is inactive.</p><p><b>CONCLUSION</b>Extract from seeds of Brassica alba can significantly inhibit mice prostatic hyperplasia induced by exterior hormone, possessing an activity of anti-androgen. Fractions I and II show an equivalent activity of total extract, which indicate that these fractions contain active components of seeds of Brassica alba which can inhibit prostatic hyperplasia.</p>