Based on the theory of blood collateral， postoperative recurrence and metastasis of bladder cancer are considered to arise primarily from the binding of stasis and toxin， which accumulate and hide within the blood collaterals. Accordingly， treatment should focus on clearing and resolving the deeply concealed stasis toxin retained in the blood collaterals. The paired use of insect and vine medicinals may exert synergistic effects by simultaneously searching out and eliminating pathogenic factors， guiding the action of herbs to the channels， and unblocking the collaterals. Drawing on clinical practice， the stasis-toxin pathogenesis of postoperative recurrence and metastasis of bladder cancer can be divided into four stages including stagnation and astringent of collateral qi， formation of fixed stasis nests， transformation of persistent stasis into toxin， and deficiency of healthy qi with lingering toxin. Accordingly， four herb pairs are proposed for each stage based on conventional treatment， which are Dilong （Pheretima）-Daxueteng （Caulis Sargentodoxae）， Shuizhi （Hirudo）-Jixueteng （Caulis Spatholobi）， Wugong （Scolopendra）-Luoshiteng （Caulis Trachelospermi）， and Quanxie （Scorpio）-Qianjinteng （stephania）. Their potential modern pharmacological mechanisms are further discussed.

OBJECTIVE To evaluate the effectiveness and safety of warfarin anticoagulation therapy guided by gene test in patients undergoing left ventricular assist device （LVAD） implantation， and to analyze the influencing factors of warfarin anticoagulation efficacy. METHODS Patients who underwent LVAD implantation at the Heart and Vascular Center of Northern Jiangsu People’s Hospital from January 2023 to October 2024 and required warfarin anticoagulant therapy were selected as the study subjects. They were divided into genetic testing group （n＝51） and empirical treatment group （n＝17） based on whether they underwent CYP2C9 and VKORC1 gene test. The gene test group was given warfarin based on the predicted dose calculated by gene test， while the empirical treatment group was given warfarin by clinical doctors based on international normalized ratio （INR） experience， all patients were given warfarin once a day. Follow-up observation was conducted for 6 months to compare the effectiveness [time in therapeutic range（TTR）， the time required to reach INR for the first time， the incidence of embolic events， the incidence of INR＜1.5 events] and safety （the incidence of major and minor bleeding events，the incidence of INR＞3.5 events） of warfarin treatment between two groups of patients. According to whether the patient’s TTR was ≥60%， they were divided into TTR≥60% group （n＝20） and TTR＜60% group （n＝48）. Univariate and multivariate binary Logistic regression analysis were used to determine the factors affecting the anticoagulant effect of warfarin in patients. RESULTS The TTR of patients in the gene test group was significantly higher than that in the empirical treatment group （P＜0.05）. The incidence of INR＜1.5 events in the gene test group was significantly lower than in the empirical treatment group （P＜0.05）. The incidence of minor bleeding events and INR＞3.5 events in the gene test group were lower than in the empirical treatment group， but the difference was not statistically significant （P＞0.05）. The results of multivariate binary Logistic regression analysis showed that gene test was an independent protective factor for warfarin anticoagulant therapy [odds ratio （OR）＝10.842， 95% confidence interval （CI）： 1.211-27.037， P＝0.033]， and the combination of statins was an independent risk factor for warfarin anticoagulant therapy [OR＝0.196， 95%CI： 0.045-0.861， P＝0.031]. CONCLUSIONS Under the guidance of gene test， warfarin anticoagulation therapy for LVAD patients after implantation can improve TTR， shorten the anticoagulation target time， and has good safety； meanwhile， it should be noted that the combination of statins may enhance the anticoagulant effect of warfarin， thereby increasing the risk of bleeding in patients.

OBJECTIVE: Benzylisoquinoline alkaloids (BIAs) have pharmacological functions and clinical use. BIAs are mainly distributed in plant species across the order Ranunculales and the genus Phellodendron from Sapindales. The BIA biosynthesis has been intensively investigated in Ranunculales species. However, the accumulation mechanism of BIAs in Phellodendron is largely unknown. The aim of this study is to unravel the biosynthetic pathways of BIAs in Phellodendron amurens. METHODS: The transcriptome and metabolome data from 18 different tissues of P. amurense were meticulously sequenced and subsequently subjected to a thorough analysis. Weighted gene co-expression network analysis (WGCNA), a powerful systems biology approach that facilitates the construction and subsequent analysis of co-expression networks, was utilized to identify candidate genes involved in BIAs biosynthesis. Following this, recombinant plasmids containing candidate genes were expressed in Escherichia coli, a widely used prokaryotic expression system. The purpose of this genetic engineering endeavor was to express the candidate genes within the bacteria, thereby enabling the assessment of the resultant enzyme activity. RESULTS: The synonymous substitutions per synonymous site for paralogs indicated that at least one whole genome duplication event has occurred. The potential BIA biosynthetic pathway of P. amurense was proposed, and two PR10/Bet v1 members, 14 CYP450s, and 33 methyltransferases were selected as related to BIA biosynthesis. One PR10/Bet v1 was identified as norcoclaurine synthase, which could catalyze dopamine and 4-hydroxyphenylacetaldehyde into (S)-norcoclaurine. CONCLUSION Our studies provide important insights into the biosynthesis and evolution of BIAs in non-Ranunculales species.

Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

ObjectiveTo clarify the anti-inflammatory and lung-protective effects of Yantiao prescription on lipopolysaccharide （LPS）-induced acute lung injury （ALI）， and to explore the impact of Yantiao prescription on the metabolic pathways of arachidonic acid （AA） in vivo. MethodsThirty male C57BL/6J mice were randomly divided into the following groups based on body weight： normal group， model group， dexamethasone group （2 mg·kg^-1）， low-dose Yantiao prescription group （18 g·kg^-1）， and high-dose Yantiao prescription group （36 g·kg^-1）， with 6 mice in each group. The ALI mouse model was established by intraperitoneal injection of LPS. The treatment groups received oral gavage once a day for 7 consecutive days， and serum and lung tissue were collected at the end of the experiment. The content of pro-inflammatory cytokines tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to assess lung tissue pathology. The wet/dry weight ratio （W/D） and myeloperoxidase （MPO） activity in lung tissue were measured. The content of AA metabolites in serum and lung tissue was measured by liquid chromatography triple quadrupole-mass spectrometry （LC-MS/MS）. ResultsCompared with the conditions in the normal group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the model group was significantly increased （P<0.01）. The alveolar structure in mice was severely damaged， with markedly thickened alveolar walls and extensive inflammatory cell infiltration. The W/D ratio and MPO activity in lung tissue were significantly increased （P<0.01）. The content of AA metabolites， including prostaglandin D₂ （PGD₂）， prostaglandin E₂ （PGE₂）， 11（S）-hydroxy-eicosatetraenoic acid ［11（S）-HETE］， and 5-hydroxy-eicosatetraenoic acid （5-HETE） in serum and lung tissue was significantly increased （P<0.05）， while the content of 11，12-epoxyeicosatrienoic acid （11，12-EET） and 14，15-epoxyeicosatrienoic acid （14，15-EET） in serum was significantly decreased （P<0.01）. Compared with the results in the model group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the dexamethasone group， low-dose Yantiao prescription group， and high-dose Yantiao prescription group was significantly reduced （P<0.05）. Mild thickening of alveolar walls， scattered inflammatory cell infiltration， and relatively intact tissue structure with improved alveolar architecture were observed. The W/D ratio and MPO activity in lung tissue were significantly reduced （P<0.01）. The content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum from the dexamethasone group was significantly decreased （P<0.05）， while the content of 14，15-EET in serum significantly increased （P<0.01）， and the content of 5-HETE in lung tissue significantly decreased （P<0.01）. In the low-dose and high-dose Yantiao prescription groups， the content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum and lung tissue was significantly decreased （P<0.05）， while the content of 11，12-EET in both serum and lung tissue was significantly increased （P<0.05）. ConclusionYantiao prescription has significant protective effects against LPS-induced ALI， which are related to its regulation of AA metabolic pathways in vivo.

Objective:To investigate gut microbiota differences between individuals with and without colorectal adenoma(CRA)and to identify gut microbes associated with CRA.Methods:This cross-sectional study analyzed the gut microbiota of 100 patients with CRA and 68 individuals without CRA(aged 40-75 years)who underwent colonoscopies between March 2021 and March 2022 at Tianjin Nankai Hospital.Fecal samples were sequenced for the V3-V4 region of the bacterial 16S rRNA gene using the Illumina NovaSeq platform.Results:Compared to the non-CRA group,the CRA group exhibited reduced relative abundances of identified and unidentified Lachnospiraceae,with increased Faecalibacterium and Streptococcus.In the non-CRA group,the relative abundances of Coprococcus,unidentified Clostridiaceae,and Clostridium were higher.LEfSe analysis revealed significant enrichment of Gammaproteobacteria,Proteobacteria,Enterobacteriales,and Faecalibacterium in the CRA group,while the non-CRA group was enriched for Moraxellaceae,Acinetobacter,and Anaerostipes.Conclusions:These findings suggest a discernible disparity in the gut microbiota structure between CRA patients and individuals without adenoma.The enrichment of potential pathogenic taxa,such as Faecalibacterium and Streptococcus,in the CRA group suggests a possible association with adenoma development.

Objective:To detect the expression level and clinical significance of centromere protein I (CENPI) in hepatocellular carcinoma (HCC) and to preliminarily explore the effects of CENPI on the biological behavior of liver cancer cells and its possible molecular mechanisms. Methods:The TCGA database, real-time fluorescent quantitative polymerase chain reaction, Western blot, and immunohistochemical staining experiments were used to analyze and detect the expression differences of CENPI in liver cancer and adjacent tissues. The correlation between CENPI expression levels and clinical pathological features were analyzed in combination with clinical data from HCC patients. The value of CENPI in the diagnosis and prognosis assessment of HCC was explored by plotting receiver operating characteristic curves and Kaplan-Meier survival curves. Furthermore, we investigated the impact of CENPI overexpression on the migration and healing capabilities of liver cancer cells using Transwell and wound healing experiments. Finally, the effects of CENPI on the epithelial-mesenchymal transition process in liver cancer cells and the potential molecular mechanisms were explored using Western blot. Comparisons between two groups were analyzed using t-tests, and comparisons among multiple groups were analyzed using one-way ANOVA. The expression of CENPI and its correlation with clinical pathological features were analyzed using the χ2 test. Results:The TCGA database analysis showed that the expression level of CENPI was significantly higher in liver cancer tissues than adjacent tissues, which was further validated by real-time fluorescent quantitative polymerase chain reaction, Western blotting, and immunohistochemical staining experiments. Combined clinical data analysis from HCC patients demonstrated that high expression of CENPI was positively correlated with the degree of tumor malignancy, T stage, and disease prognosis. The Kaplan-Meier survival curve indicated that the 5-year survival rate was significantly lower in patients with high CENPI expression compared to those with low expression. The results of the receiver operating characteristic curve further indicated that the expression level of CENPI had accurately predicted the prognosis of liver cancer patients (area under the curve=0.962). Transwell and wound healing experiment results indicated that overexpressing CENPI in Hep3B and Huh7 cells significantly increased cell migration numbers and healing rates. Further research results showed that overexpressing CENPI significantly upregulated the expression of mesenchymal cell-related marker genes: N-cadherin, Vimentin, and Snail protein, while the expression of the epithelial cell-related marker gene E-cadherin was significantly reduced. The mechanistic study revealed that when CENPI was overexpressed, the MEK and ERK phosphorylation levels and the expression of RAS protein were significantly increased compared to the control group, and the difference was statistically significant. Conclusion:The high expression of CENPI in the tissues of HCC patients is associated with poor prognosis, potentially promoting the migration of liver cancer cells and the epithelial-mesenchymal transition process by activating the RAS/MEK/ERK signaling pathway axis, suggesting that the CENPI gene may be a promising target for HCC treatment.

Objective:To explore the moderating effect of social support on the effect of occupational stress affecting job burnout, and to provide a theoretical basis for effectively reducing job burnout of medical workers.Methods:In April 2021, a cluster sampling method was adopted. Two units were randomly selected from the tertiary, secondary and primary medical institutions in Shanghai to carry out the survey. The survey was conducted by distributing electronic questionnaires online, and a total of 1963 valid questionnaires were collected. The questionnaire employed Maslach Burnout Inventory-General Survey (MBI-GS) to measure job burnout, and Job Content Questionnaire to measure occupational stress and social support. The questionnaire also collected demographic characteristics and work-related information. Mann-Whitney U test and Kruskal-Wallis H test were used for one-way analysis to test whether there was any difference in the distribution of occupational stress, job burnout, and social support on different demographic characteristics. Spearman's rank correlation coefficient was used to analyze the correlation between occupational stress, job burnout, and social support. Bootstrap method was used to analyze the moderating effect of social support on occupational stress affecting job burnout. Results:The occupational stress score was 1.232 (1.039, 1.530) , the job burnout score was 2.480 (1.560, 3.240) , and the social support score was 3.500 (3.125, 4.000) . Occupational stress, job burnout and social support were distributed differently on sex, job position, hospital level, monthly income, daily working hours, break duration per shift, and break duration between shifts ( P<0.05) . Occupational stress was positively associated with job burnout ( rs=0.49, P<0.001) , and social support was negatively associated with both occupational stress ( rs=-0.44, P<0.001) and job burnout ( rs=-0.48, P<0.001) . Social support played a moderating role in the influence of occupational stress on job burnout ( B=0.321, 95% CI: 0.216~0.426) . Conclusion:The problem of job burnout is more prominent among medical workers. In the context of enhanced social support, improving job stress condition can lead to a greater decrease in job burnout.

Non-alcoholic fatty liver disease(NAFLD)is a chronic liver disease caused by excessive lipid accumulation in the liver.Its incidence rate is increasing year by year and has become an increasingly serious public healthy problem.The pathogenesis of NAFLD is complex and has not been fully clarified at present.It is mainly related to multiple factors such as genetics,metabolism,intestinal flora and immune response.In order to explore the medication rules and mechanism of action of traditional Chinese medicine(TCM)in the treatment of NAFLD,and to provide references for the treatment of NAFLD with TCM and the research and development of new drugs,this article summarizes the TCM pathogenesis of NAFLD(such as"phlegm and blood stasis interlacing","liver depression and spleen deficiency",etc.)and modern etiology and pathogenesis(such as insulin resistance,lipid disorder,mitochondrial dysfunction,oxidative stress,etc.).The clinical research and experimental data at home and abroad in recent years were integrated to analyze the pathological process of NAFLD intervention by TCM through multiple targets,including improving insulin resistance and lipid metabolism disorders,inhibiting oxidative stress and mitochondrial dysfunction,etc.TCM has shown unique advantages in the prevention and treatment of NAFLD.However,the depth of its mechanism analysis and the level of clinical research still need to be improved.In the future,it is necessary to deepen the mechanism research by combining multi-omics technology to accelerate the modernization development of TCM.

Objective:To explore the moderating effect of social support on the effect of occupational stress affecting job burnout, and to provide a theoretical basis for effectively reducing job burnout of medical workers.Methods:In April 2021, a cluster sampling method was adopted. Two units were randomly selected from the tertiary, secondary and primary medical institutions in Shanghai to carry out the survey. The survey was conducted by distributing electronic questionnaires online, and a total of 1963 valid questionnaires were collected. The questionnaire employed Maslach Burnout Inventory-General Survey (MBI-GS) to measure job burnout, and Job Content Questionnaire to measure occupational stress and social support. The questionnaire also collected demographic characteristics and work-related information. Mann-Whitney U test and Kruskal-Wallis H test were used for one-way analysis to test whether there was any difference in the distribution of occupational stress, job burnout, and social support on different demographic characteristics. Spearman's rank correlation coefficient was used to analyze the correlation between occupational stress, job burnout, and social support. Bootstrap method was used to analyze the moderating effect of social support on occupational stress affecting job burnout. Results:The occupational stress score was 1.232 (1.039, 1.530) , the job burnout score was 2.480 (1.560, 3.240) , and the social support score was 3.500 (3.125, 4.000) . Occupational stress, job burnout and social support were distributed differently on sex, job position, hospital level, monthly income, daily working hours, break duration per shift, and break duration between shifts ( P<0.05) . Occupational stress was positively associated with job burnout ( rs=0.49, P<0.001) , and social support was negatively associated with both occupational stress ( rs=-0.44, P<0.001) and job burnout ( rs=-0.48, P<0.001) . Social support played a moderating role in the influence of occupational stress on job burnout ( B=0.321, 95% CI: 0.216~0.426) . Conclusion:The problem of job burnout is more prominent among medical workers. In the context of enhanced social support, improving job stress condition can lead to a greater decrease in job burnout.