Network pharmacology-based study on mechanism of Zhi-Huang-Zhi-Tong powder in rheumatoid arthritis treatment / 中国药理学通报

Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

Clinical analysis of 102 cases of labor induction in the third trimester on twin pregnancy / 中华妇产科杂志

Objective: To investigate the clinical characteristics of induced labor in twin pregnancy and the related factors of induced labor failure. Methods: The clinical data of twin pregnant women who underwent induced labor in Peking University Third Hospital from January 2016 to December 2022 were retrospectively analyzed. According to whether they had labor or not after induction, pregnant women were divided into the success group (pregnant women who had labor after induction, 72 cases) and the failure group (pregnant women who did not have labor after induction, 30 cases). Logistic regression was used to analyze the related factors of induction failure in twin pregnant women. Results: The parity and cervical Bishop score in the failure group were significantly lower than those in the success group, while the proportion of dichorionic diamniotic twins, assisted reproductive technology pregnancy and cervical Bishop score <6, postpartum hospital stay and total hospital stay in the failure group were significantly higher than those in the success group (all P<0.05). The proportion of induced labor by artificial rupture of membranes ± oxytocin intravenous infusion in the success group was 72.2% (52/72), which was significantly higher than that in the failure group (46.7%, 14/30; P=0.030). There were no significant differences between the two groups in the gestational age at delivery, the incidence of severe postpartum hemorrhage and blood transfusion, the amount of postpartum hemorrhage, the neonatal weight of two fetuses, the incidence of neonatal asphyxia, and the proportion of neonates admitted to the neonatal intensive care unit (all P>0.05). There were no severe perineal laceration and hysterectomy in all pregnant women. Multivariate logistic regression analysis showed that primipara (OR=3.064, 95%CI: 1.112-8.443; P=0.030) and cervical Bishop score <6 (OR=5.208, 95%CI: 2.008-13.508; P=0.001) were the independent risk factors for induction failure in twin pregnancy. Conclusions: Elective induction of labor in twin pregnancy is safe and feasible. It is helpful to improve the success rate of induction of labor by strictly grasping the timing and indications of termination of pregnancy, choosing the appropriate method of induction according to the condition of the cervix, and actively promoting cervical ripening .

Analysis on health status and influencing factors of 1353 mercury workers in Xinjiang / 中华劳动卫生职业病杂志

Objective: To investigate the health status of workers exposed to occupational mercury, and to provide the theoretical basis for formulating reasonable health monitoring and targeted protection measures. Methods: In November 2021, 1353 mercury-exposed workers who underwent occupational health examination in a hospital in Xinjiang Uygur Autonomous Region from 2018 to 2021 were collected as research subjects. By analyzing their blood pressure, electrocardiogram, blood routine, liver function and urine β2-microglobulin and urinary mercury in different gender, age, length of service, industry and enterprise scale, and the health status. And the influencing factors of urinary mercury were evaluated. Results: Among 1353 workers exposed to mercury, there were 1002 males (74.1%), the average age was (37.2±9.8) years old, and the length of service was 3.1 (2.0, 8.0) years. The abnormal rates of physical examination, blood pressure, electrocardiogram, blood routine, liver function, urinary β2-microglobulin and urinary mercury were 73.9% (1000/1353), 12.3% (166/1353), 30.2% (408/1353), 59.9% (810/1353), 32.5% (440/1353), 15.2% (205/1353) and 2.2% (30/1353), respectively. The abnormal rates of blood pressure, blood routine, liver function, urinary β2-microglobulin and urinary mercury in male workers were higher than those in female workers (P<0.05). The abnormal rates of workers' blood pressure and physical examination results increased with the increase of age and length of service, while the abnormal rate of electrocardiogram results were opposite (P<0.05). There were statistically significant differences in the abnormal rates of blood pressure, blood routine, urinary β2-microglobulin and physical examination results among workers of different enterprises and different industries (P<0.05). Multivariate logistic regression analysis showed that the workers with age ≥30 years old, microminiature enterprises, abnormal physical examination results and urinary β2-microglobulin were the susceptible population with abnormal urinary mercury (P<0.05) . Conclusion: The occupational health status of mercury workers in Xinjiang Uygur Autonomous Region is not optimistic, and the health monitoring of microminiature enterprises and older workers should be improved to effectively protect the physical and mental health of workers.

Systematic comparison of two kinds of Bufonis Venenum derived from different Bufo gargarizans subspecies based on metabolomics and antitumor activity / 中国中药杂志

This paper compared the differences between two kinds of Bufonis Venenum produced by Bufo gargarizans gargarizans and B. gararizans andrewsi, and verified the rationality of the market value orientation of Bufonis Venenum based on the zebrafish mo-del. Twenty batches of Bufonis Venenum from Jiangsu province, Hebei province, Liaoning province, Jilin province, and Liangshan, Sichuan province, including B. gargarizans gargarizans and B. gararizans andrewsi, were collected. The UHPLC-LTQ-Orbitrap-MS combined with principal component analysis was used to compare the differences between two kinds of Bufonis Venenum. According to the limiting conditions of VIP>1, FC<0.5 or FC>2.0, and peak total area ratio>1%, 9 differential markers were determined, which were cinobufagin, cinobufotalin, arenobufagin, resibufogenin, scillaredin A, resibufagin, 3-(N-suberoylargininyl)-arenobufagin, 3-(N-suberoylargininyl)-marinobufagin, and 3-(N-suberoylargininyl)-resibufogenin. The content of 20 batches of Bufonis Venenum was determined according to the Chinese Pharmacopoeia(2020 edition) by high-performance liquid chromatography, and the 2 batches of Bufonis Venenum, CS7(8.99% of total content) and CS9(5.03% of total content), with the largest difference in the total content of the three quality control indexes of the Chinese Pharmacopoeia(bufalin, cinobufagin, and resibufogenin) were selected to evaluate their anti-liver tumor activity based on the zebrafish model. The tumor inhibition rates of the 2 batches were 38.06% and 45.29%, respectively, proving that only using the quality control indexes of the Chinese Pharmacopoeia as the value orientation of Bufonis Venenum market circulation was unreasonable. This research provides data support for the effective utilization of Bufonis Venenum resources and the establishment of a rational quality evaluation system of Bufonis Venenum.

Clinical application value of Huanglian Jiedu Pills in improving syndrome of excess heat and fire toxin based on phase Ⅱ clinical trial study on plasma ATP, 4-HNE, and ACTH levels / 中国中药杂志

A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.

Content analysis and quality evaluation of main active components and mineral elements of Cynomorium songaricum in different habitats / 中国中药杂志

To clarify the content characteristics of the main active components and mineral elements of Cynomorium songaricum under different habitat conditions, and further explore the relationship between the quality of C. songaricum and habitats, this study took C. songaricum from 25 different habitats in China as the research object, and measured the contents of 8 main active components and 12 mineral elements separately. Diversity analysis, correlation analysis, principal component analysis and cluster analysis were carried out. The results showed that the genetic diversity of total flavonoids, ursolic acid, ether extract, potassium(K), phosphorus(P) and zinc(Zn) in C. songaricum was high. The coefficient of variation of crude polysaccharide, ether extract, gallic acid, protocatechuic aldehyde, catechin, epicatechin, calcium(Ca), sodium(Na), magnesium(Mg), sulfur(S), iron(Fe), manganese(Mn), selenium(Se) and nickel(Ni) were all over 36%, indicating that the quality of C. songaricum was significantly affected by habitats. There were strong synergistic and weak antagonistic effects among the contents of the 8 active components, and complex antagonistic and synergistic effects among the contents of the 12 mineral elements. Principal component analysis revealed that crude polysaccharide, ursolic acid, catechin, epicatechin and total flavonoids could be used as the characteristic components to evaluate the quality of C. songaricum, and Na, copper(Cu), Mn and Ni were the characteristic elements to evaluate the quality of C. songaricum. In cluster ana-lysis, the second group with the main active components as cluster center had better quality in terms of the content of active substances, and the second group with the mineral elements as cluster center had higher utilization potential in the exploitation of mineral elements. This study could provide a basis for resource evaluation and breeding of excellent varieties of C. songaricum in different habitats, and provide a reference for cultivation and identification of C. songaricum.

Mechanism of Xiaoer Chiqiao Qingre Granules in clearing heat and removing food stagnation in suckling rats with fever and food accumulation based on metabolomics / 中国中药杂志

Children's fever is often accompanied by food accumulation. Traditional Chinese medicine believes that removing food stagnation while clearing heat of children can effectively avoid heat damage. To systematically evaluate the efficacy of Xiaoer Chiqiao Qingre Granules(XRCQ) in clearing heat and removing food accumulation and explore its potential mechanism, this study combined suckling SD rats fed with high-sugar and high-fat diet with injection of carrageenan to induce rat model of fever and food accumulation. This study provided references for the study on the pharmacodynamics and mechanism of XRCQ. The results showed that XRCQ effectively reduced the rectal temperature of suckling rats, improved the inflammatory environment such as the content of interleukin-1β(IL-1β), interleukin-2(IL-2), interferon-γ(IFN-γ), white blood cells, and monocytes. XRCQ also effectively repaired intestinal injury and enhanced intestinal propulsion function. According to the confirmation of its efficacy of clearing heat, the thermolytic mechanism of XRCQ was further explored by non-targeted and targeted metabolomics methods based on LTQ-Orbitrap MS/MS and UPLC-QQQ-MS/MS. Non-target metabolomics analysis of brain tissue samples was performed by QI software combined with SIMCA-P software, and 22 endogenous metabolites that could be significantly regulated were screened out. MetaboAnalyst pathway enrichment results showed that the intervention mechanism was mainly focused on tyrosine metabolism, tricarboxylic acid cycle, inositol phosphate metabolism, and other pathways. At the same time, the results of targeted metabolomics of brain tissue samples showed that XRCQ changed the vitality of digestive system, and inhibited abnormal energy metabolism and inflammatory response, playing a role in clearing heat and removing food stagnation from multiple levels.

Quality of moxa with different leaf-to-moxa ratios based on correlation analysis of thermogravimetric properties, cellulose content, and microscopic characteristics of non-secretory trichomes / 中国中药杂志

The quality of moxa is a key factor affecting the efficacy of moxibustion. Traditional moxa grades are evaluated by the leaf-to-moxa ratio, but there is a lack of support from scientific data. Scanning electron microscopy(SEM), Image Pro Plus, Van Soest method, and stimultaneous thermal analysis(TGA/DSC) were used to characterize the scientific implication of the combustion differences between moxa with different leaf-to-moxa ratios(processed by crusher). The results showed that the median lengths from non-secretory trichomes(NSTs) of natural NSTs and moxa with leaf-to-moxa ratios of 3∶1, 5∶1, 10∶1, and 15∶1 were 542.46, 303.24, 291.18, 220.69, and 170.61 μm, respectively. The cellulose content of moxa increased significantly(P<0.05) with the increase in leaf-to-moxa ratio and the combustion parameters(T_i, t_i, D_i, C,-R_p,-R_v, S, D_b, and J_(total)) all showed an increasing trend. The correlation results showed that the burning properties of moxa(T_i,-R_v, t_i, and J_2) were significantly and positively correlated with cellulose content. NSTs with a length of 1-200 μm were significantly and positively correlated with J_2. NSTs with a length of 200-600 μm were significantly and positively correlated with J_1, T_(peak2), T_(peak1), and-R_v, and negatively correlated with J_(total), T_b, and t_b. As the leaf-to-moxa ratio increases, the NSTs in the moxa become shorter and the cellulose content increases, which is more conducive to ignition performance, heat release, and a milder, longer-lasting burn. The "NSTs-cellulose-TGA/DSC" quantitative evaluation method scientifically reveals the scientific connotation of the combustion of moxa with different leaf-to-moxa ratios and provides a scientific basis for the establishment of quality evaluation methods for moxa with different leaf-to-moxa ratios.

pH and GSH dual-responsive silybin nano-micelles for inhibition of breast cancer activity and metastasis in vitro / 药学学报

The clinical tumor therapy was greatly challenged due to the complex characteristics of tumor microenvironment, however, which also provide arena for novel therapeutic strategies. In this study, poly(2-ethyl-2-oxazoline)-poly(lactic acid)-SS-poly(β-amino ester (PEOz-PLA-SS-PBAE) triblock copolymers with pH and GSH double response were synthesized, polymer micelles were prepared by thin film hydration method for loading of silybin to improve its antitumor activity. The critical micelle concentration was determined by pyrene fluorescence method as 1.8 μg·mL-1. The particle size was 155.30 ± 1.80 nm as determined by dynamic light scattering, with polydispersity index of 0.168 ± 0.004. The drug loading and entrapment efficiency of the micelles were determined by HPLC as (5.48 ± 0.04)% and (68.52 ± 0.48)%, respectively. The in vitro drug release profiles showed that the micelles have low pH sensitivity and high GSH responsiveness, and exhibited sustained release profiles. The good biocompatibility of the material was proved by measuring the hemolysis rate and cytotoxicity of the blank micelle. The cytotoxicity and apoptosis rate of tumor cells showed that the drug loaded PEOz-PLA-SS-PBAE micelles had significant inhibitory effect and apoptosis-inducing effect on MDA-MB-231 cells. The results of wounding healing assay and Transwell invasion test showed that the drug loaded PEOz-PLA-SS-PBAE micelles could significantly inhibit the metastasis of MDA-MB-231 cells. The PEOz-PLA-SS-PBAE drug-loaded micelles prepared in this study have good inhibitory effect on tumor growth and anti-tumor metastasis in vitro, which lays the foundation for the further application of silybin.

Effects of KCNQ1OT1 Gene Knockout Combined with Bruceine D on Proliferation, Migration, and Invasion of Breast Cancer MDA-MB-231 Cells / 肿瘤防治研究

Objective To explore the effect of KCNQ1OT1 gene knockout combined with bruceine D on the proliferation, migration, and invasion of breast cancer MDA-MB-231 cells. Methods Cell Counting Kit-8, wound healing, and Transwell invasion assay were used to detect the effects of bruceine D and siKCNQ1OT1 on the viability, migration, and invasion of MDA-MB-231 cells. Effect of bruceine D and siKCNQ1OT1 on the expression of KCNQ1OT1 in MDA-MB-231 cells was detected by qRT-PCR. Western blot was used to detect the effect of bruceine D and siKCNQ1OT1 on the expression of EMT-related proteins and CDC42, p-MKK7, MKK7 proteins in MDA-MB-231 cells. Results Bruceine D and siKCNQ1OT1 could significantly inhibit the viability, migration, and invasion of MDA-MB-231 cells, and the inhibitory effect was enhanced when they were combined (all P < 0.05); bruceine D downregulated the expression of KCNQ1OT1 in MDA-MB-231 cells (all P < 0.05); bruceine D combined with siKCNQ1OT1 significantly decreased CDC42, p-MKK7, N-cadherin, and Vimentin expression in MDA-MB-231 cells and increased the expression of E-cadherin (all P < 0.05). Conclusion Bruceine D combined with siKCNQ1OT1 significantly inhibit the proliferation, migration, invasion, and EMT of human breast cancer MDA-MB-231 cells, and its molecular mechanism may be related to the blocking of CDC42/MKK7 signaling pathway.

Femtosecond laser assisted phacoemulsification combined with anterior vitrectomy for the treatment of pediatric cataract / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the clinical outcomes of femtosecond laser-assisted cataract phacoemulsification combined with anterior vitrectomy in the treatment of pediatric cataracts.METHODS: Retrospective study. A total of 10 patients(17 eyes)diagnosed as pediatric cataract in Foshan Aier Eye Hospital from January 2021 to September 2022 were collected, including 5 males(9 eyes)and 5 females(8 eyes), with an age of 3～9(4.50±1.20)years old. All children underwent femtosecond laser assisted phacoemulsification combined with anterior vitrectomy. The visual acuity, intraocular pressure and pigment deposits of intraocular lens(IOL)surface, synechia and hyperplasia of posterior capsule lens at 1wk, 1 and 6mo postoperatively were observed during the 6mo follow-up.RESULTS: All surgical procedures were successful, and there was no serious complication intraoperatively or postoperatively. BCVA(LogMAR)was 0.63±0.18 preoperatively and 0.42±0.10, 0.32±0.09, and 0.22±0.08 at 1wk, 1 and 6mo postoperatively(all P&#x003C;0.001). There was no difference in the comparison of intraocular pressure at different times of surgery(P=0.125). There was no statistically significant difference in the incidence of IOL surface pigment deposits, synechia, and posterior capsule lens hyperplasia at different times after surgery(P&#x003E;0.05). The incidence of IOL surface pigment deposits at 1wk, 1 and 6mo after surgery was 3 eyes(18%), 1 eye(6%), and 1 eye(6%), respectively, the incidence of synechia was 0 eye, 1 eye(6%), 2 eyes(12%), and the incidence of posterior capsule lens hyperplasia was 0 eye, 0 eye, and 2 eyes(12%), respectively.CONCLUSION: Femtosecond laser-assisted cataract phacoemulsification combined with vitrectomy for the removal of the anterior vitreous can effectively prevent anterior capsular tear and the occurrence of posterior capsule opacification.

Practice of structured electronic medical record design and quality management / 中华医院管理杂志

In order to assist in the standardization and maturity evaluation of national hospital information interconnection, and further standardize the application and management of hospital medical record data, a hospital carried out the practice of design of structured medical records and the corresponding quality management from April 2021. Based on the six sigma quality management method, the hospital had developed universal templates for electronic medical records and a list of candidate electronic medical record templates. The problems faced by medical record data had been analyzed, and improvement strategies had been proposed from three levels: template design, software functionality and management services. The clinical departments were guided to design and develop various structured electronic medical record templates for specialties and specialized diseases, and established a medical record template design and quality management method. The hospital had ultimately designed a total of 614 structured electronic medical record templates that met the actual needs of the hospital. This practice enhanced the scalability of structured templates and quality of the data, and achieved localization and specialization of medical record templates while meeting the requirements of information interconnection and sharing, providing reference for promoting the interconnection and sharing of electronic medical records of hospitals in China.

A retrospective study correlating the prognoses and hospitalization costs of stroke survivors with dysphagia / 中华物理医学与康复杂志

Objective:To seek any correlation between and prognosis and hospitalization costs of stroke survivors with dysphagia.Methods:The records of 1370 stroke survivors admitted to the rehabilitation departments of 3 public hospitals in Weifang were studied. Of them, 499 (36.4%) were diagnosed with dysphagia and 871 were not. Binary logistic regression and multiple linear regression were employed to analyze the correlation between dysphagia and the occurrence of pneumonia, modified Rankin Scale (mRS) scores, modified Barthel index (MBI) scores, length of stay and total hospitalization cost.Results:After adjusting for confounding factors, the risk of pneumonia in the dysphagia group was 2.4 times higher. At discharge, the risk of an mRS≥3 was 3.3 times greater and that of an MBI score <60 was 1.7 times greater with dysphagia. Multiple stepwise linear regression showed that dysphagia was significantly associated with higher mRS scores at discharge, lower MBI scores, and longer hospital stays. The standardized regression coefficients predict that after the length of stay, dysphagia is the strongest predictor of the cost of hospitalisation, followed by ADL ability, pneumonia, supratentorial, haemorrhagic stroke and CCI.Conclusions:Dysphagia is a significant predictor of the hospitalization costs of stroke patients. It is recommended to identify and treat dysphagia as early as possible to improve the prognosis of such patients and reduce the economic burden.

Preparation，characterization，in vitro drug release property and cytotoxicity of Periplaneta americana extract-loaded spider fibroin membrane / 中国药房

OBJECTIVE To prepare spider fibroin membrane loaded with Periplaneta americana extract， and investigate its characterization， in vitro drug release property and cytotoxicity. METHODS Using natural spider silk collected from Chilobrachys guangxiensis as raw material， P. americana extract as model drug， the drug-loaded spider fibroin membrane （hereinafter referred to as drug-loaded membrane） was prepared by solvent casting method. The material matrix spider fibroin membrane without P. americana extract （hereinafter referred to as blank membrane） was prepared with same method. The membrane structure was characterized by static water contact angle， Fourier infrared chromatography， X-ray diffraction and scanning electron microscopy from different angles； drug release characteristics in artificial saliva were simulated in vitro to evaluate the drug sustained-release performance. MTT assay was adopted to validate the cytotoxicity of drug-loaded membrane. RESULTS The drug-loaded membrane was prepared， and the static water contact angle was less than 90°， which was less than that of blank membrane. The drug-loaded membrane showed the characteristic absorption peak to polypeptide of P. americana extract at 1 500-1 700 cm－1. X-ray diffraction and scanning electron microscopy also proved that the drug was successfully loaded into the pellicle. The release time of the pellicle in artificial saliva was more than 200 min. The MTT test results showed that the cell proliferation rates of blank membrane and drug-loaded membrane were 84.6% and 79.4% （both greater than 70%）， respectively， without significant potential cytotoxicity. CONCLUSIONS Drug-loaded membrane prepared with natural spider silk has a certain sustained-release effect in artificial saliva， which can be further developed as a drug sustained-release carrier with excellent biological characteristics and biocompatibility.

The therapeutic effect of Balanophora polysaccharide on acetic acid gastric ulcer in rats and its mechanism / 中国药理学通报

Aim To study the therapeutic effect of Balanophora polysaccharide(BPS)on gastric ulcer(GU)induced by acetic acid in rats and to investigateits mechanisms. Methods Sixty male SD rats were randomly divided into sham-operated group, GU model group, omeprazole positive group(3.6 mg·kg-1), and low, medium and high dose of BPS treatment groups(100, 200 and 400 mg·kg-1). The GU model group was prepared by acetic acid cautery method, and the morphology and pathological changes of ulcers were observed by visual observation combined with HE staining, and the ulcer area and inhibition rate were measured and calculated; superoxide dismutase(SOD)activity, malondialdehyde(MDA)content and glutathione peroxidase(GSH-PX)activity were measured by enzymatic assay; tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)content were detected by ELISA. The expression levels of epidermal growth factor(EGF)and epidermal growth factor receptor(EGFR)were measured by immunohistochemistry staining and Western blot. Results Compared with the sham-operated group, obvious ulcer damage was seen in the model group. Compared with the model group, the BPS-treated group showed a significant reduction in ulcer area, an increase in SOD and GSH-PX activity and EGF and EGFR expression levels, and a significant decrease in MDA, TNF-α and IL-6 content. Conclusions BPS has a therapeutic effect on GU in rats, and its mechanism may be related to the inhibition of oxidative stress, suppression of inflammatory stimuli and promotion of regenerative repair of gastric mucosa.

Effects of total saponins from Trillium tschonoskii maxim on cognition impairment and mitochondrial autophagy in aging rats induced by D-Gal / 中国药理学通报

Aim To investigate the effects of total saponins from Trillium tschonoskii maxim(TST)on cognitive impairment and mitochondrial autophagy in aging rats induced by D-galactose(D-gal). Methods Male SD rats were randomly divided into normal control group,model group(D-gal,subcutaneous injection),intervention group(TST,low,medium and high dose groups by intragastric administration),with 10 rats in each group,and administered for 6 weeks. Morris water maze was used to evaluate the cognitive function. HE and Nissl staining were used to test the hippocampal and brain cortex morphology. Immunohistochemistry staining was applied to detect the localization expression of Pink1 and Parkin. Western blot was employed to detect the expressions of Pink1,Parkin,LC3-Ⅱ,p62 and Beclin1. Results Compared with the normal control group,the escape latency time was prolonged and the number of crossing platform decreased in D-gal model group(P<0.05). The number of neurons in hippocampus significantly decreased. The positive cells labeled by Pink1 and Parkin staining in hippocampus significantly decreased. The expressions of Pink1,Parkin,LC3-Ⅱ and Beclin1 were markedly reduced,while the expression of p62 was significantly raised(P<0.05). Compared with D-gal model group,the escape latency time of TST dose groups was shortened,the Times of crossing the platform was more,and the time of staying in the platform quadrant increased(P<0.05). The number of neurons in hippocampus significantly increased. The positive cells labeled by Pink1 and Parkin staining in hippocampus significantly increased. The expressions of Pink1,Parkin,LC3-Ⅱ and Beclin1 in hippocampus were apparently up-regulated,while the protein expression of p62 was evidently down-regulated(P<0.05). Conclusions TST has neuroprotective effects on the learning and memory capacities in aging rats induced by D-gal,which may be related to the increasing levels of Pink1,Parkin,LC3-Ⅱ and Beclin1 proteins and the activation of mitochondrial autophagy.

Research progress on regulatory mechanism of long non-coding RNA CYTOR in human cancer / 中国药理学通报

Cancer is difficult to cure because of its heterogeneity, drug resistance and easy recurrence and metastasis. Revealing the molecular mechanism of cancer genesis and development, identifying new diagnostic markers and molecular therapeutic targets are undoubtedly effective strategies to solve the problems of early diagnosis, treatment and improvement of prognosis of cancer patients. More and more studies have shown that long non-coding RNA (IncRNA) is specifically expressed in human cancer and is a key regulator of cancer occurrence and development. Cytoskeleton regulator RNA (CYTOR) is a carcinogenic lncRNA found in recent years. CYTOR is highly expressed in many types of cancer and regulates the development of cancer through a variety of pathways, which may be an effective biomarker for early cancer diagnosis, molecular targeted therapy and prognosis assessment. This paper reviews the molecular regulatory mechanism and related biological characteristics of CYTOR in human cancer, in order to provide new scientific reference for clinical cancer diagnosis and treatment.

Molecular mechanism of microRNAs regulating sorafenib resistance in hepatocellular carcinoma / 中国药理学通报

Hepatocellular carcinoma (HCC) is one of the most deadly malignancies in the world, with strong invasiveness, low cure rate, high metastasis rate and poor prognosis. Sorafenib is the most important and effective first-line drug for the treatment of advanced hepatocellular carcinoma, but its clinical efficacy is severely limited by primary and acquired drug resistance. Mi-crornas ( micrornas) are small non-coding Rnas that play a key regulatory role in the occurrence and development of hepatocellular carcinoma and the progression of sorafenib resistance. This paper summarizes the role of micrornas in the initiation and development of sorafenib resistance in hepatocellular carcinoma, in order to further understand the mechanism of sorafenib anti-hep-atocellular carcinoma, and to provide valuable theoretical basis for clinical targeted therapy and prognosis improvement in hepatocellular carcinoma.

Association between maternal plasma one-carbon biomarkers during pregnancy and fetal growth in twin pregnancies / 中华妇产科杂志

Objective: To characterize the relationship between the levels of plasma methyl donor and related metabolites (including choline, betaine, methionine, dimethylglycine and homocysteine) and fetal growth in twin pregnancies. Methods: A hospital-based cohort study was used to collect clinical data of 92 pregnant women with twin pregnancies and their fetuses who were admitted to Peking University Third Hospital from March 2017 to January 2018. Fasting blood was collected from the pregnant women with twin pregnancies (median gestational age: 18.9 weeks). The levels of methyl donors and related metabolites in plasma were quantitatively analyzed by high-performance liquid chromatography combined with mass spectrometry. The generalized estimation equation was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and neonatal outcomes of twins, and the generalized additive mixed model was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and fetal growth ultrasound indicators. Results: (1) General clinical data: of the 92 women with twin pregnancies, 66 cases (72%) were dichorionic diamniotic (DCDA) twin pregnancies, and 26 cases (28%) were monochorionic diamniotic (MCDA) twin pregnancies. The comparison of the levels of five plasma methyl donors and related metabolites in twin pregnancies with different basic characteristics showed that the median levels of plasma choline and betaine in pregnant women ≥35 years old were higher than those in pregnant women <35 years old, and the differences were statistically significant (all P<0.05). (2) Correlation between plasma methyl donor and related metabolites levels and neonatal growth indicators: after adjusting for confounding factors, plasma homocysteine level in pregnant women with twins was significantly negatively correlated with neonatal birth weight (β=-47.9, 95%CI:-94.3- -1.6; P=0.043). Elevated methionine level was significantly associated with decreased risks of small for gestational age infants (SGA; OR=0.5, 95%CI: 0.3-0.9; P=0.021) and low birth weight infants (OR=0.6, 95%CI: 0.4-0.9; P=0.020). Increased homocysteine level was associated with increased risks of SGA (OR=1.5, 95%CI: 1.0-2.2; P=0.029) and inconsistent growth in twin fetuses (OR=1.9, 95%CI: 1.0-3.7; P=0.049). (3) Correlation between the levels of plasma methyl donors and related metabolites and intrauterine growth indicators of twins pregnancies: for every 1 standard deviation increase in plasma choline level in pregnant women with twin pregnancies, fetal head circumference, abdominal circumference, femoral length and estimated fetal weight in the second trimester increased by 1.9 mm, 2.6 mm, 0.5 mm and 20.1 g, respectively, and biparietal diameter, abdominal circumference and estimated fetal weight increased by 0.7 mm, 3.0 mm and 38.4 g in the third trimester, respectively, and the differences were statistically significant (all P<0.05). (4) Relationship between plasma methyl donor and related metabolites levels in pregnant women with different chorionicity and neonatal birth weight and length: the negative correlation between plasma homocysteine level and neonatal birth weight was mainly found in DCDA twin pregnancy (β=-65.9, 95%CI:-110.6- -21.1; P=0.004). The levels of choline, betaine and dimethylglycine in plasma of MCDA twin pregnancy were significantly correlated with the birth weight and length of newborns (all P<0.05). Conclusion: Homocysteine level is associated with low birth weight in twins, methionine is associated with decreased risk of SGA, and choline is associated with fetal growth in the second and third trimesters of pregnancy.

Evaluation of the clinical manifestations of COVID-19 in patients with aplastic anemia undergoing immunosuppressive therapy: a prospective cohort study (NICHE) / 中华血液学杂志

Objective: To investigate the clinical features of coronavirus disease 2019 (COVID-19) in patients with aplastic anemia (AA) undergoing immunosuppressive therapy (IST) . Methods: In this prospective cohort study, we collected the demographic and clinical data of patients with AA and COVID-19 from December 1, 2022, to January 31, 2023. We described the clinical features of COVID-19 among patients with AA and evaluated the effects of IST on the signs and severity of COVID-19. Results: A total of 170 patients with AA and COVID-19 were included. The common early symptoms, including fever, dizziness or headache, muscle or body aches, and sore throat, disappeared within 1-2 weeks. Approximately 25% of the patients had persistent fatigue within 2 weeks. Many patients experienced cough after an initial 1-3 days of infection, which lasted for more than 2 weeks. There were no differences in the duration of total fever episodes and maximum body temperature when patients were stratified according to whether or not they underwent IST, by IST duration, or by use of anti-lymphocyte globulin (ALG) (P>0.05). No differences were observed in the occurrence of symptoms in either the early or recovery stages when patients with AA were stratified according to whether or not they underwent IST, or by IST duration (P>0.05). However, patients who received ALG had fewer fever episodes within 1 week after infection (P=0.035) and more sore throat episodes within 2 weeks after infection (P=0.015). There were no other significant differences in clinical symptoms between patients who did and patients who did not receive ALG (P>0.05) . Conclusion: The majority of patients with AA and COVID-19 recovered within 2 weeks of noticing symptoms when treated with IST.