Biological Connotation of Pathogenesis of Ulcerative Colitis with Liver Depression and Spleen Deficiency Based on Bile Acid-intestinal Flora Axis / 中国实验方剂学杂志

Ulcerative colitis （UC） is one of the chronic refractory inflammatory bowel diseases characterized by abdominal pain， diarrhea， and mucus， pus and blood in the stool. In recent years， with changes in human life style and improvements of the diagnosis， the incidence and prevalence of UC have been increasing. The pathogenesis of UC is closely related to intestinal mucosal immune dysfunction， intestinal flora disturbance， and abnormal bile acid secretion. Patients with UC have abnormal bile acid secretion and intestinal flora imbalance. A large number of studies have found that abnormal bile acid secretion inhibits immune function， affects signal transduction， and destroys the intestinal mucosal barrier. Intestinal flora disturbance has an important impact on the occurrence and development of inflammation， immune homeostasis， and stress. Bile acids indirectly or directly affect the structure and function of intestinal flora， and at the same time， they produce secondary bile acids under the modification of intestinal flora， entering the liver through enterohepatic circulation. Therefore， the complex dialogue mechanism of bile acid-intestinal flora axis is closely related to the occurrence and development of UC. Based on the basic theory of traditional Chinese medicine（TCM） and clinical research， it is found that emotion is an important factor that induces this disease， spleen and stomach weakness is the root of the disease， and liver depression and spleen deficiency are the key pathogenesis of UC. Combined with modern medicine and molecular biology research， it is believed that abnormal secretion of bile acids is a microscopic manifestation of liver depression in TCM， and intestinal flora disturbance is the biological basis of spleen deficiency. In the pathogenesis of UC， the imbalanced bile acid-intestinal flora axis is consistent with the pathogenesis of liver depression and spleen in TCM. The exploration of the biological connotation of the pathogenesis of UC with liver depression and spleen deficiency from the perspective of bile acid-intestinal flora axis can better explain the scientific nature of its pathogenesis， which provides new clinical solutions and reliable references for studying the pathogenesis of UC with liver depression and spleen deficiency and finding representative prescriptions to prevent and treat this disease.

Influencing factors of delayed elimination of methotrexate in children with acute lymphoblastic leukemia treated by high-dose methotrexate and their prognostic analysis / 白血病·淋巴瘤

Objective:To investigate the influencing factors of delayed methotrexate (MTX) elimination after high-dose methotrexate (HD-MTX) treatment in children with acute lymphoblastic leukemia (ALL) and the effects of delayed MTX elimination and HD-MTX reduction on the prognosis of children with ALL.Methods:The clinical data of 242 children with ALL diagnosed and treated in Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2015 to June 2020 in accordance with the Chinese Children's Cancer Group study ALL 2015 (CCCG-ALL 2015) were retrospectively analyzed. Low risk and intermediate/high risk children respectively received 3 g/m 2 and 5 g/m 2 HD-MTX for 4 times, and the serum MTX concentration was monitored. The serum MTX concentration > 1 μmol/L at 44 h of administration was considered as the delayed elimination, which was divided into mild (> 1 μmol/L and ≤ 5 μmol/L), moderate (> 5 μmol/L and ≤ 10 μmol/L) and severe (> 10 μmol/L) delayed elimination. Univariate and multivariate logistic regression analysis were used to analyze the influencing factors of delayed MTX elimination, and univariate Cox proportional hazards model was used to analyze the related factors of ALL relapse. Results:The 242 children with ALL completed 962 times of HD-MTX chemotherapy. The median serum MTX concentration [ M ( Q1, Q3)] at 44 h of administration was 0.45 μmol/L (0.33 μmol/L, 0.72 μmol/L). The total incidence of delayed MTX elimination was 17.7% (170/962). The incidence of mild, moderate and severe delayed elimination was 13.8% (133/962), 2.6% (25/962) and 1.2% (12/962), respectively. Logistic regression analysis showed that age ≥ 7 years old ( OR = 1.68, 95% CI 1.17-2.41, P = 0.005), MTX dose >3 g/m 2 at each course ( OR = 2.14, 95% CI 1.52-3.03, P < 0.001) and the first course of HD-MTX chemotherapy ( OR = 2.05, 95% CI 1.43-2.93, P < 0.001) were independent risk factors for delayed MTX elimination. The median follow-up time was 50 months (34 months, 68 months), 12.8% (31/242) of the children relapsed, and the median relapse time was 30 months (30 months, 39 months). Univariate Cox regression analysis showed that there were no significant differences in the relapse rates among children with different gender, immunophenotype, risk, the number of delayed MTX elimination, and the completion of HD-MTX chemotherapy (the ratio of MTX average dose to initial planned dose) (all P > 0.05). Conclusions:The independent risk factors of delayed elimination of MTX in children with ALL are age ≥ 7 years old, MTX dose > 3 g/m 2 at each course and the first course of HD-MTX chemotherapy. Delayed elimination of MTX and reduction of HD-MTX have no significant effect on ALL relapse.

HucMSC-Ex alleviates inflammatory bowel disease via the lnc78583-mediated miR3202/HOXB13 pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

As a group of nonspecific inflammatory diseases affecting the intestine, inflammatory bowel disease (IBD) exhibits the characteristics of chronic recurring inflammation, and was proven to be increasing in incidence (Kaplan, 2015). IBD induced by genetic background, environmental changes, immune functions, microbial composition, and toxin exposures (Sasson et al., 2021) primarily includes ulcerative colitis (UC) and Crohn's disease (CD) with complicated clinical symptoms featured by abdominal pain, diarrhea, and even blood in stools (Fan et al., 2021; Huang et al., 2021). UC is mainly limited to the rectum and the colon, while CD usually impacts the terminal ileum and colon in a discontinuous manner (Ordás et al., 2012; Panés and Rimola, 2017). In recent years, many studies have suggested the lack of effective measures in the diagnosis and treatment of IBD, prompting an urgent need for new strategies to understand the mechanisms of and offer promising therapies for IBD.

Discussion on the Idea to Establish Standardized Construction Standard System for “Internet+TCM Pharmacy ” Based on Questionnaire Survey / 中国药房

OBJECTIVE：To provide reference for establishing stan dardized construction standard system of “internet+TCM pharmacy”. METHODS ： Questionnaire through literature review ， investigation and expert consultation were compiled. A questionnaire survey was carried out among TCM staff to understand the current situation and problems of “internet + TCM pharmacy”in Chinese medical institutions. Based on the results of the questionnaire ，a frame of standardized construction standard system for “internet+TCM pharmacy ”was tried to constructed. RESULTS & CONCLUSIONS：A total of 74 questionnaires were distributed and 74 were returned ，including 1 invalid questionnaire ，with an effective rate of 98.65％. Among the 73 respondents， more than 60％ were from TCM hospitals ，or with the title of vice senior or above ，and 55（75.3％）were national TCM characteristic technology inheritance talents. The survey results showed that more than 80％ of TCM pharmacies in medical institutions were equipped with full-time reviewers ，provided decocting service ，set up decocting room ，and carried out distribution service，and could achieve the same-day or part of the same-day delivery. More than half of the respondents believed that the prescriptions of TCM decoction pieces in their medical institutions were issued in strict accordance with the relevant requirements ， the rational drug use monitoring software was used ，and the error analysis of relevant work links was carried out regularly ， prescription coping training was regularly carried out for dispensers ，and decoction knowledge and operation process training were carried out for decoction personnel. However ，the vast majority of respondents （67，accounting for 91.8％）thought that their medical institutions only used traditional methods to control and evaluate the quality of finished decoction products. The results of the evaluation of the importance of 6 links and 17 key points of operation showed that the highest concentration of opinions was the quality of decoction pieces ，and the key points of operation were special drug treatment. The results of principle component analysis and maximum variance analysis showed that current construction of “internet+TCM pharmacy ”was mainly reflected in the two dimensions as TCM decocting ，consultation and distribution servi ces. Statistical analysis indicated that there were significant differences in staff training ，awareness of laws and policies ， regular error analysis ，patient satisfaction survey ，optimization of payment and consulting services among different levels and categories institutions （P＜0.05）. It was necessary to carry out the standardization construction of “internet+TCM pharmacy”. It is suggested that the standard system for standardized construction of“Internet + TCM pharmacy ”should be established from 5 aspects：basic construction conditions ，the standardization of procurement and acceptance ，the standardization of dispensing ，the standardization of decocting and distribution service and the standardization of pharmaceutical consultation services.

Clinical study of self-made Chaimu-Xingnao Decoction combined with rehabilitation training in the treatment of cognitive dysfunction after stroke / 国际中医中药杂志

Objective:To evaluate the clinical effects of self-made Chaimu-Xingnao Decoction combined with rehabilitation training in the treatment of cognitive dysfunction after stroke. Methods:A total of 82 stroke patients with cognitive dysfunction who met the inclusion criteria in Haikou Hospital of Traditional Chinese Medicine from January 2015 to December 2018 were divided into two groups according to random number table method, 41 in each group. The control group was treated with rehabilitation training on the basis of routine treatment, and the observation group was given self-made Chaimu-Xingnao Decoction on the basis of the control group. Both groups were treated for 12 weeks. The cognitive function of the patients was evaluated by neurobehavioral cognitive status examination (NCSE). The whole high blood viscosity, whole low blood viscosity, plasma viscosity, hematocrit and fibrinogen were detected by automatic hemorheology tester, and the levels of nerve growth factor (NGF) and neurotrophic factor (NTF) were detected by ELISA. The clinical efficacy was evaluated. Results:The total clinical effective rate of the observation group was 90.2% (37/41), which was significantly higher than 70.7% (29/41) of the control group, and the difference was statistically significant ( χ2=4.970, P=0.026). After treatment, the NCSE score in the observation group was significantly higher than that of the control group ( t=3.689, P<0.01), the whole high blood viscosity, whole low blood viscosity, plasma viscosity, hematocrit and fibrinogen in the observation group were significantly lower than those in the control group ( t values were 12.406, 14.638, 10.947, 12.546 and 8.451, respectively, all Ps<0.001), the serum NGF (119.82 ± 16.73 pg/ml vs. 93.31 ± 15.20 pg/ml, t=7.510) and NTF (5.58 ± 0.59 ng/ml vs. 4.01 ± 0.52 ng/ml, t=12.783) level in the observation group were significantly higher than those in the control group ( P<0.01). There were no serious adverse reactions during treatment in both groups. Conclusions:Self-made Chaimu-Xingnao Decoction combined with rehabilitation training can improve the hemorheology index, regulate the level of nerve cell factor and improve the clinical effect of patients with cognitive dysfunction after stroke.

Clinical study of Qixie-Huoxue-Tongluo decoction combined with ozagrel sodium injection in treatment of cerebral thrombosis / 国际中医中药杂志

Objective@#To study the clinical efficacy of Qixie-Huoxue-Tongluo decoction combined with ozagrel sodium injection in treatment of cerebral thrombosis.@*Methods@#According to the random number table method, 91 cerebral thrombosis patients who met the inclusion criteria were divided into the control group (45 cases) and the study group (46 cases). The control group was treated with ozagrel sodium injection on the basis of routine treatment, while the study group was treated with Qixie-Huoxue-Tongluo decoction on the basis of the control group. The two groups were treated for 7 days. The National Institute of Health Stroke Scale (NIHSS)was used to assess the degree of neurological impairment, the Activity of Daily Living (ADL) was used to assess the quality of life; and the levels of MDA, SOD, NO, neuron-specific enolase (NSE) and neuronal protein (S-100β)were detected by ELISA.The clinical efficacy was evaluated.@*Results@#The total effective rate was 93.5% (43/46) in the study group and 71.1% (32/45) in the control group, there was significant difference between the two groups (χ2=7.853, P=0.005). After treatment, the NIHSS score in the study group was significantly lower than that in the control group (16.1 ± 5.0 vs. 20.3 ± 5.3; t=3.889, P<0.01), and the ADL score in the study group (51.9 ± 9.3 vs. 45.3 ± 8.6, t=3.461) was significantly higher than that in the control group (P<0.01); the serum level of MDA (3.10 ± 0.48 mmol/L vs. 4.25 ± 0.76 mmol/L, t=11.427) and NO (41.14 ± 6.74 U/L vs. 62.20 ± 8.43 U/L, t=10.028) in the study group were significantly lower than those in the control group (P<0.01), the SOD (204.36 ± 21.29 vs. 163.39 ± 17.45, t=13.177) level in the study group was significantly higher than that of the control group (P<0.01); the serum NSE (4.85 ± 1.03 μg/L vs. 7.93 ± 1.14 μg/L, t=13.529) and S-100β protein (0.18 ± 0.03 μg/L vs. 1.02 ± 0.15 μg/L, t=37.232) levels in the study group were significantly lower than those in the control group (P<0.01).@*Conclusions@#Qixie-Huoxue-Tongluo decoction combined with ozagrel sodium injection can improve the degree of neurological impairment in patients with cerebral thrombosis, improve the quality of life clinical efficacy. And the mechanism may be related to inhibition of lipid peroxidation, anti-free radicals and so on.

Clinical study of Qixie-Huoxue-Tongluo decoction combined with ozagrel sodium injection in treatment of cerebral thrombosis / 国际中医中药杂志

Objective To study the clinical efficacy of Qixie-Huoxue-Tongluo decoction combined with ozagrel sodium injection in treatment of cerebral thrombosis. Methods According to the random number table method, 91 cerebral thrombosis patients who met the inclusion criteria were divided into the control group (45 cases) and the study group (46 cases). The control group was treated with ozagrel sodium injection on the basis of routine treatment, while the study group was treated with Qixie-Huoxue-Tongluo decoction on the basis of the control group. The two groups were treated for 7 days. The National Institute of Health Stroke Scale (NIHSS)was used to assess the degree of neurological impairment, the Activity of Daily Living (ADL) was used to assess the quality of life; and the levels of MDA, SOD, NO, neuron-specific enolase (NSE) and neuronal protein (S-100β)were detected by ELISA.The clinical efficacy was evaluated. Results The total effective rate was 93.5% (43/46) in the study group and 71.1% (32/45) in the control group, there was significant difference between the two groups (χ2=7.853, P=0.005). After treatment, the NIHSS score in the study group was significantly lower than that in the control group (16.1 ± 5.0 vs. 20.3 ± 5.3; t=3.889, P<0.01), and the ADL score in the study group (51.9 ± 9.3 vs. 45.3 ± 8.6, t=3.461) was significantly higher than that in the control group (P<0.01); the serum level of MDA (3.10 ± 0.48 mmol/L vs. 4.25 ± 0.76 mmol/L, t=11.427) and NO (41.14 ± 6.74 U/L vs. 62.20 ± 8.43 U/L, t=10.028) in the study group were significantly lower than those in the control group (P<0.01), the SOD (204.36 ± 21.29 vs. 163.39 ± 17.45, t=13.177) level in the study group was significantly higher than that of the control group (P<0.01); the serum NSE (4.85 ± 1.03 μg/L vs. 7.93 ± 1.14 μg/L, t=13.529) and S-100β protein (0.18 ± 0.03 μg/L vs. 1.02 ± 0.15 μg/L, t=37.232) levels in the study group were significantly lower than those in the control group ( P<0.01). Conclusions Qixie-Huoxue-Tongluo decoction combined with ozagrel sodium injection can improve the degree of neurological impairment in patients with cerebral thrombosis, improve the quality of life clinical efficacy. And the mechanism may be related to inhibition of lipid peroxidation, anti-free radicals and so on.

Protective effect of n-3 polyunsaturated fatty acids on acute skin photodamage in SKH-1 mice / 中华皮肤科杂志

Objective To evaluate the protective effect of dietary n-3 polyunsaturated fatty acids (PUFA) on ultraviolet-induced acute skin photodamage in SKH-1 hairless mice,and to explore its mechanism.Methods Totally,50 SKH-1 hairless mice were equally divided into 5 groups to be fed with forages with the ratios of n-3 PUFA to fatty acid being 0,12.5％,25％,50％ and 100％ respectively (control group,12.5％,25％,50％ and 100％ n-3 PUFA groups).On day 8 after feeding,the back of mice in the 5 groups were irradiated by a solar ultraviolet simulator at 2 minimum erythema doses (MED) to establish an acute photodamage model.After 24 hours,cutaneous reactions on the back of mice were observed by naked eyes and dermoscopy,and skin biopsy specimens were subjected to hematoxylin and eosin (HE) staining for observing the epidermal structure,intercellular edema,inflammatory cell infiltration and photodamaged cells.Immunohistochemical staining was performed to determine the expression of inflammatory cytokines including interleukin-1 beta (IL-1β),IL-6 and tumor necrosis factor alpha (TNF-α),and enzyme-linked immunosorbent assay (ELISA) to measure the protein expression of the above 3 inflammatory cytokines in the tissue homogenate.Results Compared with the control group and 12.5％ n-3 PUFA group,the 25％,50％ and 100％ n-3 PUFA groups all showed a milder degree of acute skin photodamage,epidermis thickening,intercellular edema,and inflammatory cell infiltration.The number of photodamaged cells per high-power field (× 100) was significantly higher in the control group and 12.5％ n-3 PUFA group (17.50 ± 4.93,14.25 ± 1.71,respectively) than in the 25％,50％ and 100％ n-3 PUFA groups (6.50 ± 1.73,4.75 ± 2.06,4.50 ± 1.73,respectively;F =19.1,P ＜ 0.001).Immunohistochemical results showed that IL-1β,IL-6 and TNF-α were expressed to different extents in the epidermis and dermis among the 5 groups at 24 hours after ultraviolet radiation.Compared with the control group and 12.5％ n-3 PUFA group,the 25％,50％ and 100％ n-3 PUFA groups showed significantly lower expression of the above 3 inflammatory cytokines (P ＜ 0.001).ELISA revealed that the levels of IL-1β,IL-6 and TNF-α in the skin tissues of the mice were significantly lower in the 25％,50％ and 100％ n-3 PUFA groups than in the control group and 12.5％ n-3 PUFA group (P ＜ 0.05).Conclusions When the ratio of n-3 PUFA to fatty acid reaches more than 25％,dietary n-3 PUFA has protective effects against ultraviolet-induced acute photodamage,.Moreover,the higher the content of n-3 PUFA is,the stronger the protective effect is.It is suggested that n-3 PUFA may inhibit the inflammatory reaction through the arachidonic acid pathway.

Effects of photodynamic therapy alone or in combination with antifungal agents on the apoptosis of planktonic and biofilm cells of Exophiala dermatitidis / 中华皮肤科杂志

Objective To evaluate the in vitro effects of photodynamic therapy alone or in combination with antifungal agents on the apoptosis of planktonic and biofilm cells of Exophiala dermatitidis (E.dermatitidis).Methods The planktonic suspensions of E.dermatitidis were prepared,and the biofilms of E.dermatitidis were prepared via a modified 96-well plate-based methods.Planktonic and biofilm cells of E.dermatitidis were separately divided into several groups:antifungal agent groups treated with antifungal agents alone,photodynamic therapy group receiving photodynamic therapy alone,combination groups receiving photodynamic therapy followed by the treatment with antifungal agents,and blank control group receiving no treatment.These antifungal agents included amphotericin B,posaconazole,voriconazole and itraconazole.The concentrations of these antifungal agents were all 1 mg/L,and the treatment with antifungal agents lasted 2 hours.Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to detect the apoptosis of planktonic and biofilm cells of E.dermatitidis in all the groups.Results The antifungal agents and photodynamic therapy both affected the apoptosis of planktonic (both P ＜ 0.001) and biofilm cells (beth P ＜ 0.05) of E.dermatitidis.The apoptosis rates of E.dermatitidis planktonic cells in the control group,amphotericin B group,posaconazole group,voriconazole group and itraconazole group were 11.67％ ± 0.21％,13.30％ ± 1.78％,14.30％ ± 3.61％,14.51％ ± 1.91％and 36.17％ ± 4.00％ respectively.The apoptosis rate of E.dermatitidis planktonic cells was significantly higher in the itraconazole group than in the control group (P ＜ 0.05),but no significant differences were observed between the other 3 antifungal agent groups and control group (all P ＞ 0.05).The photodynamic therapy group also showed a significantly higher apoptosis rate of E.dermatitidis planktonic cells (41.37％ ±7.80％) compared with the control group (P ＜ 0.05).After the treatment with photodynamic therapy combined with amphotericin B,posaconazole,voriconazole or itraconazole,the apoptosis rates of E.dermatitidis planktonic cells were 29.23％ ± 6.71％,37.23％ ± 10.86％,43.57％ ± 6.42％ and 69.87％ ± 3.53％ respectively.Moreover,the photodynamic therapy + voriconazole group and photodynamic therapy + itraconazole group both showed significantly higher apoptosis rates compared with the voriconazole group and itraconazole group respectively (both P ＜ 0.05).The apoptosis rate of E.dermatitidis biofilm cells was significantly higher in the photodynamic therapy group than in the control group (32.00％ ± 0.43％ vs.25.30％ ± 1.31％,P ＜ 0.05),as well as in the photodynamic therapy + amphotericin B than in the amphotericin B group (P ＜ 0.05).Conclusion Photodynamic therapy combined with antifungal agents can markedly promote the apoptosis of planktonic and biofilm cells of E.dermatitidis.

Studies on the Chemical Constituents of Tripterygium Wilfordii / 中国药师

Objective:To study the chemical constituents in the roots of Tripterygium wilfordii. Methods: The compounds from Tripterygium wilfordii were isolated and purified by silica gel, Sephadex LH-20 and prep-HPLC chromatography, and their structures were elucidated based on the physiochemical properties and spectroscopic analysis. Results:Twelve compounds were isolated and iden-tified as wilforgine(1),wilforine(2),triptonoterpene methyl ether(3),glut-5-en-3β,28-diol(4),wilforol E(5),triptobenzene L (6),maytenoic acid(7),triptophenolide(8),celastrol(9),demethylzeylasteral(10),1-desacetyl wilforgine(11) and wilfortrine (12). Conclusion:The 1D and 2D NMR data of 1 and 2 are assigned for the first time,and the absolute configurations of 1 are con-firmed by X-ray single crystal diffraction.

Expression of VEGF, NRP1 and cancer stem cell marker CD44 in gastric carcinoma and their correlations / 临床与实验病理学杂志

Purpose To investigate the expression of VEGF, NRP1 and the cancer stem cell marker CD44 in gastric carcinoma and their correlations. Methods High throughput technology of tissue microarray and immunohistochemical SP method were employed to investigate the expression of VEGF, NRP1 and CD44 proteins in 72 gastric carcinoma specimens and 52 normal gastric tissues. Immu-nohistochemistry records were reviewed, their correlations and the clinicopathological characteristics were evaluated. Results ( 1 ) The positive rates of VEGF, NRP1 and CD44 proteins were 76. 4%, 66. 7%, and 83. 3% in gastric carcinoma, respectively, with sig-nificant differences from normal gastric tissues (P<0. 01). (2) The positive expression of VEGF and NRP1 were closely correlated with infiltration depth, lymph node metastasis and TNM stage (P<0. 05). The positive expression of CD44 was closely correlated with Lauren type, differentiation degree, lymph node metastasis and TNM stage (P<0. 05). (3) In addition, the expression of CD44 was significantly correlated with VEGF and NRP1 in gastric carcinoma (rs =0. 578, rs =0. 278, rs =0. 316, P<0. 05). Conclusions VEGF, NRP1 and the cancer stem cell marker CD44 are highly expressed in gastric cancer, which are closely related to the biological behaviors of gastric cancer. Synergistic effects are observed between VEGF and NRP1, and they are closely related to the expression of the cancer stem cell marker CD44, which remains to be further studied.