Four novel β-galactoside prodrugs were designed and synthesized from anthraquinones HAQ-OH and AQ-OH in an attempt to use the prodrugs to selectively release superoxide anion (O2−) in cancer cells and to achieve selected anticancer activity by utilizing the Warburg effect and the elevated level of β-galactosidase in certain cancer cells. Cellular assays showed that the prodrugs Gal-HAQ and Gal-AQ selectively inhibited the proliferation and induced apoptosis of ovarian cancer OVCAR-3 cells overexpressing β-galactosidase. Using O2− fluorescent probe, it was found that in OVCAR-3 cells Gal-HAQ and Gal-AQ could time-dependently release O2−, which was essential for their anticancer activity. Furthermore, it was found that Gal-HAQ and Gal-AQ were effective senolytics toward senescent cells overexpressing β-galactosidase without affecting the viability of corresponding non-senescent cells, further confirming the β-galactosidase-dependent cytotoxicity of the prodrugs. In conclusion, Gal-HAQ and Gal-AQ, which release O2− in response to β-galactosidase, are expected to serve as candidate prodrugs targeting cancer cells.

Small intestinal bacterial overgrowth（SIBO）is a clinically common but poorly recognized disease with clinical symptoms that overlap with those of functional gastrointestinal disorders（FGID）. FGID is a common risk factor for the occurrence of SIBO，and its SIBO incidence rate is significantly higher than that of healthy people，and has a certain correlation. Intestinal microbiota dysbiosis（including SIBO）plays an important role in the pathophysiology of FGID. At present，the diagnosis and treatment of SIBO still face challenges，and the treatment plan of FGID is gradually introduced into the treatment of SIBO. SIBO and FGID are closely related in clinical manifestations，incidence rate，pathophysiology，treatment and other aspects，but there is little research on the relationship between them. Prospective and large-scale clinical research is still needed to improve understanding and diagnostic accuracy.This article reviews the research progress on the relationship between SIBO and FGID.

Objective To observe the clinical efficacy of therapy of resolving blood stasis and tranquilizing mind in the treatment of insomnia with internal blockage of blood stasis type.Methods A parallel randomized controlled trial was conducted on 88 cases of insomnia patients with internal blockage of blood stasis type who admitted to Bao'an Traditional Chinese Medicine Hospital Affiliated to Guangzhou University of Chinese Medicine from January 2024 to June 2024.The patients were randomly divided into an observation group and a control group,with 44 cases in each group.The observation group was treated with the self-made Huayu Anshen Prescription(modified Xuefu Zhuyu Decoction)orally following the therapy of resolving blood stasis and tranquilizing mind,while the control group was treated with Dexzopiclone Tablets orally.The course of treatment for the two groups covered four weeks.The changes in the scores of traditional Chinese medicine(TCM)syndrome,Pittsburgh Sleep Quality Index(PSQI),Self-Rating Depression Scale(SDS),and Self-Rating Anxiety Scale(SAS)in the two groups before and after treatment were observed,and then the clinical efficacy and medication safety of the patients in the two groups were evaluated.Results(1)After four weeks of treatment,the total effective rate of the observation group was 86.36%(38/44)and that of the control group was 70.45%(31/44),and the intergroup comparison showed that the clinical efficacy of the observation group was significantly superior to that of the control group,the difference being statistically significant(χ2=8.080,P<0.05).(2)After treatment,the scores of TCM syndrome,PSQI,SDS,and SAS of patients in the two groups were all significantly decreased compared with those before treatment(P<0.01),and the decrease in the observation group was significantly superior to that in the control group,the differences all being statistically significant(P<0.05).(3)During the treatment,there were no obvious adverse reactions occurred in the two groups,with higher safety.Conclusion Therapy of resolving blood stasis and tranquilizing mind for treating insomnia with internal blockage of blood stasis type can effectively alleviate patients'clinical symptoms,improve their sleep quality and relieve depression and anxiety,with stronger clinical efficacy and higher safety.

Objective To investigate the clinical efficacy of Xiaozhi Tea(composed of Eupatorii Herba,Nelumbinis Folium,Chrysanthemi Flos,Cassiae Semen,Crataegi Fructus,bran-fried Atractylodis Macrocephalae Rhizoma,Poria,Pseudostellariae Radix,Citri Reticulatae Pericarpium,Glycyrrhizae Radix et Rhizoma Praeparata cum Melle)combined with Atorvastatin Calcium Tablets for the treatment of hyperlipidemia patients with turbid phlegm obstruction syndrome.Methods A retrospective cohort study was conducted in 200 hyperlipidemia patients with turbid phlegm obstruction syndrome who visited the outpatient department of Shenzhen Bao'an Traditional Chinese Medicine Hospital Group from September 2023 to September 2024.The patients were equally divided into a trial group and a control group based on the treatment regimen,with 100 cases in each group.The control group received oral use of Atorvastatin Calcium Tablets alone,while the trial group received Xiaozhi Tea in addition to Atorvastatin Calcium Tablets orally,both groups were treated for 8 weeks.Changes in traditional Chinese medicine(TCM)syndrome scores and lipid profiles of total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)There were 3 patients in the control group dropping out due to lack of follow-up data,leaving 197 patients who eventually completed the study,100 cases in the trial group and 97 cases in the control group.(2)After 8 weeks of treatment,the total effective rate in the trial group was 97.00%(97/100)and that in the control group was 87.63%(85/97).The intergroup comparison(tested by chi-square test)showed that the trial group showed significantly stronger efficacy than the control group(P＜0.05).(3)Both groups exhibited significant reductions in TCM syndrome scores after treatment in comparison with those before treatment(P＜0.05),and a more pronounced reduction was presented in the trial group(P＜0.05).(4)Both groups showed decreased TC,TG,and LDL-C levels(P＜0.05)and increased HDL-C level after treatment in comparison with those before treatment(P＜0.05).The trial group demonstrated more obvious reduction of TC,TG,LDL-C,and more obvious elevation of HDL-C than the control group(P＜0.05).(5)In terms of safety,no severe adverse reactions occurred in either group.The incidence of adverse reactions in the trial group was 1.00%(1/100)and that in the control group was 2.06%(2/97),with no statistically significant difference between groups(P＞0.05).Conclusion Xiaozhi Tea combined with Atorvastatin Calcium Tablets exerts certain efficacy in treating hyperlipidemia with turbid phlegm obstruction syndrome,and is effective on significantly improving lipid profiles and clinical symptoms.The combination therapy demonstrates superior efficacy compared to Atorvastatin Calcium Tablets alone.

[Objective] To investigate the correlation between human leukocyte antigen (HLA) gene polymorphism and hepatitis B virus (HBV) infection. [Methods] Venous blood samples were collected from 501 healthy individuals undergoing physical examinations at Yan’an Hospital in Kunming, Yunnan Province. Enzyme linked immunosorbent assay (ELISA) was used to detect HBV halves. Based on the results of HBV half detection, the patients were divided into three groups: HBV carrier group, previous infection group, and healthy control group. The HLA-A antigen genotype was detected using polymerase chain reaction with sequence specific primers (PCR-SSP) genotyping technology, and the distribution frequency of HLA-A gene polymorphism was compared between HBV carrier group and healthy control group, as well as between previous infection group and healthy control group. SPSS17.0 software was used for data statistical analysis. [Results] In the healthy control group, the HLA-A2 positivity rate was 47.49%, and the allele frequency was 31.29%.The overall frequency of gene distribution in the healthy control group was consistent with the HLA-A allele table commonly and confirmed in China published by the Chinese Bone Marrow Bank. The HLA-A2 positivity rate and allele frequency in the HBV carrier group were 63.04% and 42.23%, respectively; The difference in HLA-A2 positivity rate and allele frequency among carriers was statistically significant (P<0.05). the HLA-A2 positivity rate and allele frequency in the HBV previous infection group were 56.14% and 35.97%, respectively, which did not significantly differ from those in the healthy control group (P>0.05). [Conclusion] HLA-A2 gene may be a susceptibility gene for chronic hepatitis B HBV carriers.

Objective To investigate the dietary patterns of rural residents in the high-incidence areas of esophageal cancer (EC), and to explore the clustering and influencing factors of risk factors associated with high-incidence characteristics. Methods A special structured questionnaire was applied to conduct a face-to-face survey on the dietary patterns of rural residents in Yanting county of Sichuan Province from July to August 2021. Univariate and multivariate logistic regression models were used to analyze the influencing factors of risk factor clustering for EC. Results There were 838 valid questionnaires in this study. A total of 90.8% of rural residents used clean water such as tap water. In the past one year, the people who ate fruits and vegetables, soybean products, onions and garlic in high frequency accounted for 69.5%, 32.8% and 74.5%, respectively; the people who ate kimchi, pickled vegetables, sauerkraut, barbecue, hot food and mildew food in low frequency accounted for 59.2%, 79.6%, 68.2%, 90.3%, 80.9% and 90.3%, respectively. The clustering of risk factors for EC was found in 73.3% of residents, and the aggregation of two risk factors was the most common mode (28.2%), among which tumor history and preserved food was the main clustering pattern (4.6%). The logistic regression model revealed that the gender, age, marital status and occupation were independent influencing factors for the risk factors clustering of EC (P<0.05). Conclusion A majority of rural residents in high-incidence areas of EC in Yanting county have good eating habits, but the clustering of some risk factors is still at a high level. Gender, age, marital status, and occupation are influencing factors of the risk factors clustering of EC.

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Recently,the substance P(SP)/neurokinin-1 receptor(NK-1R)system has been found to be involved in various human pathophysiological disorders including the symptoms of coronavirus disease 2019(COVID-19).Besides,studies in the oncological field have demonstrated an intricate correlation between the upregulation of NK-1R and the activation of SP/NK-1R system with the progression of multiple carcinoma types and poor clinical prognosis.These findings indicate that the modulation of SP/NK-1R system with NK-1R antagonists can be a potential broad-spectrum antitumor strategy.This review updates the latest potential and applications of NK-1R antagonists in the treatment of human diseases and cancers,as well as the underlying mechanisms.Furthermore,the strategies to improve the bioavailability and efficacy of NK-1R antagonist drugs are summarized,such as solid dispersion systems,nanonization,and nanoencapsulation.As a radiopharmaceutical therapeutic,the NK-1R antagonist aprepitant was originally developed as radioligand receptor to target NK-1R-overexpressing tumors.However,combining NK-1R antagonists with other drugs can produce a synergistic effect,thereby enhancing the therapeutic effect,alleviating the symptoms,and improving patients'quality of life in several diseases and cancers.

Objective To study the regulation effects of Bazhen Decoction combined with Baizhu Fuzi Decoction on glucose metabolism and estrogen level in rats with polycystic ovary syndrome.Methods The rat model of polycystic ovary syndrome was established by subcutaneous injection of human chorionic gonadotropin(HCG)combined with insulin.Rats were randomly divided into the polycystic ovary syndrome group,the Baizhu Fuzi Tang group(6.4 g/kg),the Bazhen Tang group(9.2 g/kg),the Bazhen Tang combined with Baizhu Fuzi Tang group(11.55 g/kg)and the diethylstilbestrol group(0.5 mg/kg).A blank control group(unmodulated rats)was set up with 10 rats in each group.The uterine index of rats was determined and calculated.Fasting blood glucose(FBG),2 h postprandish blood glucose(2 h PBG)and fasting insulin(FINS)were determined and insulin sensitivity index(ISI)and insulin resistance index(IR)were calculated.Serum estradiol(E2),testosterone(T),luteinizing hormone(LH),follicle stimulating hormone(FSH),prolactin(PRL),anti-Mullerian tube hormone(AMH)and insulin-like growth factor 1(IGF-1),C-reactive protein(CRP),interleukin(IL)-6,tumor necrosis factor(TNF)-α,total peroxidase activity(T-AOC),superoxide dismutase(SOD)and malondialdehyde(MDA)levels in ovarian tissue were detected by enzyme-linked immunosorbent assay(ELISA).The pathological changes of ovarian tissue were detected by hematoxylin-eosin(HE)staining.Real-time quantitative polymerase chain reaction(qPCR)was used to determine mRNA levels of ARA70,CBP,SCR1 and HOXA10 in endometrium and mRNA expressions of AMPK,GLUT4 and PPARγ in ovarian tissue.Western blot assay was used to determine expression levels of AMPK,GLUT4 and PPARγ in ovarian tissue.Results Compared with the polycystic ovary syndrome group,uterine index,FINS,FBG,2 h PBG,IR levels,serum T,LH,FSH,PRL,AMH,IGF-1 levels,ovarian tissue CRP,IL-6,TNF-α,T-AOC and MDA level,endometrial ARA70,CBP,SCR1 mRNA level of rats decreased significantly in the Baizhu Fuzi decoction group,the Bazhen decoction group and the Bazhen decoction combined with Baizhu Fuzi decoction group(P＜0.05).ISI level,serum E2 level,ovarian tissue SOD level,endometrial HOXA10 mRNA level,ovarian tissue AMPK,GLUT4 and PPARγ mRNA and protein levels were significantly increased(P＜0.05).The above indexes were significantly changed in the Bazhen decoction and Bazhu Fuzi decoction group than those of the Bazhu Fuzi decoction group and the Bazhen decoction group(P＜0.05).Conclusion Bazhen Decoction combined with Baizhu Fuzi Decoction can regulate glucose metabolism,inhibit ovarian tissue oxidation and inflammatory damage,improve endometrium tolerance,regulate estrogen level,and improve the progression of polycystic ovary syndrome in rats.The mechanism may be related to the regulation of AMPK/GLUT4/PPARγ pathway.