OBJECTIVE: Huachansu injection (HCSI), a promising anti-cancer Chinese medicine injection, has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer (CRC) patients. The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan (CPT-11). METHODS: To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11, we measured changes in the biological behavior of LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) expression was investigated in the CPT-11-induced colitis mouse model. Subsequently, we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3 (OATP1B3) in HepG2 cells. RESULTS: The combination index (CI) results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect (CI < 1), which significantly suppressing the LoVo cell migration, enhancing G2/M and S phase arrest, and inhibiting tumor growth in vivo. Additionally, the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model, while the increased expression of UGT1A1 in HepG2 cells and in mouse was observed. CONCLUSION The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect. The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components. The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.
Irinotecan/therapeutic use* ; Animals ; Glucuronosyltransferase/genetics* ; Humans ; Colorectal Neoplasms/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Nude ; Mice ; Up-Regulation/drug effects* ; Male ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Hep G2 Cells ; Cell Line, Tumor ; Intestines/drug effects* ; Amphibian Venoms

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Objective To investigate the effect of quercetin on HCE-2 injury of human corneal epithelial cells induced by high osmotic pressure and its mechanism.Methods HCE-2 cells were randomly divided into control group(normal osmotic pressure),model group(high osmotic pressure),experimental-L group(high osmotic pressure+31.25 pg·mL-1 quercetin),experimental-M group(high osmotic pressure+62.50 μg·mL-1 quercetin),experimental-H group(high osmotic pressure+125.00 μg·mL-1 quercetin),erastin group(high osmotic pressure+125.00 μg·mL-1 quercetin+30.00 μmol·L-1 iron death inducer erastin).Cell survival rate was detected by cell counting kit 8;reactive oxygen species(ROS)levels was detected by C11-BODIPY 581/591 probe staining;glutathione(GSH)and malondialdehyde(MDA)levels were determined by kit method;the expression levels of glutathione peroxidase 4(GPX4),dihydrolactate dehydrogenase(DHODH)and ferroptosis suppressor protein 1(FSP1)were detected by real-time quantitative polymerase chain reaction and Western blot.Results The cell survival rates of control group,model group,experimental-H group and erastin group were(100.00±3.97)％,(50.05±5.83)％,(86.35±7.35)％and(58.32±4.66)％,respectively;ROS levels were 1.00±0.09,2.45±0.16,1.19±0.05 and 2.09±0.30,respectively;GPX4 protein levels were 1.09±0.11,0.34±0.03,0.91±0.12 and 0.30±0.04,respectively;FSP1 protein levels were 0.92±0.06,0.25±0.03,0.89±0.07 and 0.39±0.07,respectively;DHODH protein levels were 0.89±0.11,0.31±0.04,0.86±0.11,0.41±0.04,respectively.Compared with model group,the above indexes in control group were statistically significant(all P＜0.05);the differences between experimental-H group and model group were statistically significant(all P＜0.05);the above indexes in erastin group were significantly different from those in experimental-H group(all P＜0.05).Conclusion Quercetin can ameliorate HCE-2 cell damage induced by high osmotic pressure by inhibiting iron death pathway.

Objective To investigate the predictive value of systemic immune-inflammation index(SII)and N-terminal pro-brain natriuretic peptide(NT-proBNP)level in elderly patients with acute ST-segment elevation myocardial infarction(STEMI)developing contrast-induced acute kidney injury(CIAKI)after PCI.Methods A total of 1085 elderly STEMI patients undergoing emergency PCI in the Affiliated Hospital of Xuzhou Medical University from January 2018 to March 2023 were consecutively recruited as a training set,and another 287 elderly STEMI pa-tients receiving emergency PCI in the East Branch of the Affiliated Hospital from January 2021 to June 2023 were included as a verification set.According to the diagnostic criteria of CIAKI,they were divided into CIAKI group(n=95)and non-CIAKI group(n=990).Based on the results of restricted cubic spline(RCS)analysis,the patients from the training set were assigned into low-risk subgroup(n=292),moderate-risk group(n=515)and high-risk group(n=278).Multivari-ate logistic regression analysis was used to analyze the independent risk factors of CIAKI in elder-ly STEMI patients after PCI,and ROC curve was plotted to analyze the predictive value of combi-nation of SII and NT-proBNP.The risk of CIAKI was compared among the patients at different risk grades.Results Age,SII,baseline serum creatinine,NT-proBNP,fasting blood glucose and use of diuretics were independent risk factors for CIAKI after primary PCI in elderly STEMI patients(P＜0.05,P＜0.01).The AUC value of SII combined with NT-proBNP in predicting CIAKI was 0.801(95％CI:0.761-0.842,P＜0.01),with a sensitivity of 83.2％and a specificity of 67.5％,both superior to that of SII or NT-proBNP alone.RCS analysis revealed an increased risk of CIAKI at SII ≥1084.97 × 109/L and NT-proBNP ≥296.12 ng/L.The incidence of CIAKI was increased with the increase of risk grades(1.71％vs 6.41％vs 20.50％).Conclusion SII and NT-proBNP are independent risk factors for CIAKI after emergency PCI in elderly STEMI pa-tients.And their combination has better predictive value for CIAKI.

Plague,caused by Yersinia pestis,is a zoonotic disease that infects both humans and animals.Y.pestis not only encodes various virulence factors that can disrupt host immune signaling but also can modify its lipopolysaccharide(LPS)struc-ture,thereby evading host immune surveillance and potently suppressing the host's immune response,in an important molecu-lar mechanism underlying its high pathogenicity.The LPS of Y.pestis lacks an O antigen,and its lipid A structure possesses a unique temperature transition regulatory mechanism.At different temperatures,Y.pestis forms lipid A with different numbers of acyl side chains,which plays a pivotal role in the evasion of host innate immune recognition and clearance.Here,we present a comprehensive review of research progress in the biosynthetic regulation,structural variation,and immune escape mechanism of Y.pestis LPS,to provide a reference for the study of the molecular mechanisms of pathogens using LPS structural modifica-tions to elude host innate immune defenses.

Objective To explore the acupoint selection rules of acupuncture treatment for cerebellar ataxia using data mining techniques.Methods Taking the related literature of acupuncture treatment of cerebellar ataxia as the retrieval content,the computer retrieval of China National Knowledge Internet(CNKI),China Biomedical Literature Database(SinoMed),Wanfang Data Knowledge Service Platform(Wanfang),China Science and Technology Journal Database(VIP),American Biomedical Information Retrieval System(PubMed)and other major databases.The eligible acupoints in the literature were entered into the Microsoft Excel 2021 software table to establish a database of acupoints frequency,meridian tropism,specific acupoints,distribution sites and other information for acupuncture treatment of cerebellar ataxia.SPSS Modeler 18.0 Apriori algorithm,SPSS Statistics 25.0 and SPSS Modeler 18.0 Web complex network were used to analyze the association rules of the included prescription acupoints,Ward cluster analysis and draw the tree diagram and the Web network diagram of high-frequency acupoints and core prescriptions.Results(1)A total of 93 articles were included,including 117 acupuncture prescriptions and 172 acupoints,with a total frequency of 1 199 times of acupoints.(2)The top 10 acupoints were Fengchi(GB20),Zusanli(ST36),Hegu(LI4),Baihui(DU20),Sanyinjiao(SP6),Taichong(LR3),Quchi(LI11),Yanglingquan(GB34),Wangu(GB12),and Tianzhu(BL10).(3)The top five meridians used frequently were gallbladder meridian of foot shaoyang,governor vessel(GV),stomach meridian of foot yangming,large intestine meridian of hand yangming and bladder meridian of foot taiyang.(4)The selection of acupoints is mainly based on the head,face,neck and lower limbs.(5)The highest frequency of the use of specific points is the intersection point.(6)The high-frequency acupoints for acupuncture treatment of cerebellar ataxia are Fengchi-Wangu,Fengchi-Tianzhu and Fengchi-Tianzhu-Wangu.The top 31 high-frequency acupoints(frequency＞10 times)can be divided into nine effective clusters.Conclusion Acupuncture treatment for cerebellar ataxia has formed a compatibility rule with the main principle of"regulating the mind and constraining the bones,extinguishing wind and stopping the movement",with the far and near acupoints as the main body,and attaches importance to the application of yang meridians with multiple qi and blood,presenting the basic acupoint prescription with Fengchi-Wanggu-Tianzhu as the core.

Objective To understand the serotype,molecular typing and drug sensitivity characteristics of Salmonella isolated from food and stool samples of diarrhea patients in Nan'an District of Chongqing.Methods A total of 71 Salmonella strains isolated from food and stool samples of diarrhea patients in Nan'an District of Chongqing from 2019 to 2022 were serotyped,and the drug resistance of the strains was determined by the micro-broth dilution method.Multilocus sequence typing(MLST)was performed on 2 Salmonella Ken-tucky strains,and whole genome sequencing was performed on 8 Salmonella typhimurium strains and 2 Sal-monella typhimurium variants.Results The 71 strains of Salmonella included 13 serotypes.A total of 48 Sal-monella strains were isolated from stool samples of diarrhea patients,with Salmonella typhimurium(56.25％,27/48)and Salmonella enteritidis(18.75％,9/48)as the main serotypes.A total of 23 Salmonella strains were isolated in food samples,with Salmonella Rissen(26.09％,6/23)as the predominant.The total drug re-sistance rate of 71 strains of Salmonella was 97.18％.The highest drug resistance rate was ampicillin(69.01％),followed by tetracycline(64.79％),compound sulfamethoxazole(43.66％)and chloramphenicol(43.66％).The multidrug resistant strains accounted for 61.97％(44/71),including 60.42％(29/48)of stool samples of diarrhea patients and 65.22％(15/23)of food samples.The two Salmonella Kentucky strains iso-lated from food and diarrhea patients were resistant to 7 and 8 types,respectively,with the largest number of drug resistant types in the corresponding samples.The MLST types of both Salmonella Kentucky strains was ST198 type.The MLST types of 8 Salmonella typhimurium strains selected for sequencing were ST19,and the MLST types of 2 Salmonella typhimurium monophasic variants were ST34.The genetic relationship of Salmo-nella typhimurium with the same ST type was different.Conclusion The serotypes of Salmonella isolated from Nan'an District of Chongqing are diverse and the drug resistance is serious.The detection of ST198 Sal-monella Kentucky is more accurate by using whole genome sequencing than MLST.The surveillance of Sal-monella serotypes,molecular typing and drug resistance should be strengthened.

Objective This study aimed to evaluate the associations of serum folate and/or vitamin B12 concentrations with obesity among Chinese children and adolescents. Methods A cross-sectional study was conducted including 3,079 Chinese children and adolescents,aged 6 to 17 years,from Jiangsu,China.Anthropometric indices,such as,children's body mass index(BMI),BMI z-scores,waist circumference,and waist-to-height ratio were utilized.Multivariable linear regression and generalized additive models were used to investigate the associations of serum folate and vitamin B12 levels with anthropometric indices and odds of obesity. Results We observed that serum vitamin B12 concentrations were inversely associated with all anthropometric indices and the odds of general obesity[odds ratio(OR)= 0.68;95%confidence interval(CI)= 0.59,0.78]and abdominal obesity(OR = 0.68;95%CI = 0.60,0.77).When compared to participants with both serum vitamin levels in the two middle quartiles,those with both serum folate and vitamin B12 levels in the highest quartile were less prone to general(OR = 0.31,95%CI = 0.19,0.50)or abdominal obesity(OR = 0.46,95%CI = 0.31,0.67).Conversely,participants with vitamin B12 levels in the lowest quartile alongside folate levels in the highest quartile had higher odds of abdominal obesity(OR = 2.06,95%CI = 1.09,3.91). Conclusion Higher serum vitamin B12 concentrations,but not serum folate concentrations,were associated with lower odds of childhood obesity.Children and adolescents with high levels of vitamin B12 and folate were less likely to be obese.

Objective Hydroquinone(HQ),one of the phenolic metabolites of benzene,is widely recognized as an important participant in benzene-induced hematotoxicity.However,there are few relevant proteomics in HQ-induced hematotoxicity and the mechanism hasn't been fully understood yet. Methods In this study,we treated K562 cells with 40 μmol/L HQ for 72 h,examined and validated protein expression changes by Label-free proteomic analysis and Parallel reaction monitoring(PRM),and performed bioinformatics analysis to identify interaction networks. Results One hundred and eighty-seven upregulated differentially expressed proteins(DEPs)and 279 downregulated DEPs were identified in HQ-exposed K562 cells,which were involved in neutrophil-mediated immunity,blood microparticle,and other GO terms,as well as the lysosome,metabolic,cell cycle,and cellular senescence-related pathways.Focusing on the 23 DEGs and 5 DEPs in erythroid differentiation-related pathways,we constructed the network of protein interactions and determined 6 DEPs(STAT1,STAT3,CASP3,KIT,STAT5B,and VEGFA)as main hub proteins with the most interactions,among which STATs made a central impact and may be potential biomarkers of HQ-induced hematotoxicity. Conclusion Our work reinforced the use of proteomics and bioinformatic approaches to advance knowledge on molecular mechanisms of HQ-induced hematotoxicity at the protein level and provide a valuable basis for further clarification.

Objective To observe the effects of moxibustion on myocardial pathological morphology,α-smooth muscle actin(α-SMA)and chromosome 10 deletion phosphatase and tensin homologous protein(PTEN)/mammalian target of rapamycin(mTOR)signalling pathway in rats with chronic heart failure(CHF),and to explore the possible mechanism of moxibustion in attenuating myocardial fibrosis in rats with CHF.Methods According to the random number table method,60 male SD rats were divided into the normal group(n=10)and the surgery group(n=50),and the rats in the surgery group were ligated the left coronary artery to replicate the CHF model.According to the random number table method,40 successfully modelled rats were divided into the model group,the moxibustion group,the bpV(phen)group,and the moxibustion+bpV(phen)group,with 10 rats in each group.The normal and model groups were not given any intervention;in the moxibustion group,customized moxa sticks were used to moxibrate the bilateral"Feishu"(BL13)and"Xinshu"(BL15)on the back of the rats for 30 min at each point once a day;the bpV(phen)group was injected intraperitoneally with the bpV(phen)solution(0.15 mg/kg)twice a week;the moxibustion+bpV(phen)group was based on the bpV(phen)group,and moxibustion was applied according to the moxibustion group.The intervention was carried out for 4 weeks.The general conditions of rats,such as feeding and activity were observed;HE staining was used to detect morphological changes of the cardiomyocytes;Masson staining was used to detect myocardial fibrosis;the cardiac echocardiography was used to detect ejection fraction(EF)and fractional shortening(FS);real-time PCR was used to detect the mRNA expressions of PTEN and mTOR in the cardiac muscle tissues;protein expressions of PTEN,mTOR,α-SMA in rat myocardial tissue were detected by Western blotting.Results Compared with the normal group,rats in the model group had altered cardiomyocyte morphology,severe damage to myocardial fiber structure,significantly lower EF,FS,and mTOR mRNA and protein expressions,and significantly higher PTEN,α-SMA protein expressions and PTEN mRNA expression(P<0.05).Compared with the model group,myocardial ultrastructural damage was attenuated in the moxibustion group,bpV(phen)group,and moxibustion+ bpV(phen)group,and EF,FS,and mRNA and protein expressions of mTOR were significantly higher,α-SMA protein expression was significantly lower,and mRNA and protein expressions of PTEN were significantly lower(P<0.05).Compared with the moxibustion+bpV(phen)group,myocardial ultrastructural damage was worsen in the moxibustion and bpV(phen)groups,with significantly lower EF,FS,and mRNA and protein expressions of mTOR,significantly higher α-SMA protein expression,and significantly higher mRNA and protein expressions of PTEN(P<0.05).Conclusion Moxibustion can improve the pathological morphology and function of cardiomyocytes and attenuate myocardial fibrosis in rats with CHF,and its mechanism may be related to the down-regulation of PTEN expression,and then the up-regulation of mTOR expression.